Medscape is available in 5 Language Editions – Choose your Edition here.


Hypertriglyceridemia Treatment & Management

  • Author: Mary Ellen T Sweeney, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
Updated: Apr 13, 2015

Approach Considerations

Even without a definitive diagnosis from the workup, treatment of presumed dysbetalipoproteinemia may proceed, because other lipid disorders, such as type IIb hyperlipidemia produce similar elevations in cholesterol and triglyceride levels and will respond to the same medical interventions.

In general, lifestyle modifications (eg, smoking cessation, diet, exercise, weight reduction) are initiated before any pharmacologic therapy in the treatment of primary and secondary dyslipidemia, particularly in patients who are asymptomatic.[41, 31, 37, 42, 38] Weight reduction and a diet low in saturated fat and cholesterol are advocated. Patients should avoid alcohol and estrogen in certain types of hyperlipoproteinemias.

The patient’s low-density lipoprotein (LDL) cholesterol level response is measured in 6 weeks to 6 months, depending on the patient's cardiovascular risk factors. Consider an LDL cholesterol goal of less than 70 mg/dL in patients with established coronary artery disease (CAD) or CAD risk equivalents, including clinical manifestations of noncoronary forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and carotid artery disease, transient ischemic attacks or stroke of carotid origin or 50% obstruction of a carotid artery), diabetes, or a Framingham 10-year CAD risk score of greater than 20%.[43]

Consider pharmacologic therapy if the LDL-C level remains above the following thresholds[43] :

  • Patients with low risk, 190 mg/dL or greater
  • Patients with moderate risk, 160 mg/dL or greater
  • Patients with moderately high risk, 130 mg/dL (option 100 mg/dL) or greater
  • Patients with high risk, 100 mg/dL (option 70 mg/dL) or greater

Because of the possibility of adverse effects and the question of whether the triglyceride level is an independent risk factor for atherosclerosis, many physicians use drugs to reduce the triglyceride level only when the level exceeds 500 mg/dL. Patients with triglyceride concentrations greater than 1000 mg/dL should receive diet and drug therapy and be closely monitored to prevent pancreatitis.

Patients first should be treated for the metabolic condition that is causing or exacerbating their hyperlipidemia. If diabetes is present, glucose levels and glycosylated hemoglobin (HbA1c) should be normalized with treatment that meets or exceeds the guidelines of the American Diabetes Association (ADA), if possible. If hypothyroidism is diagnosed, thyroid stimulating hormone (TSH) should be normalized.

In managing secondary dyslipidemia, consider statin therapy for all patients, as these agents reduce mortality and coronary heart disease/atherosclerotic cardiovascular disease (CHD/ASCVD) endpoints.[41] High-potency statins (atorvastatin, rosuvastatin) at high doses have greater efficacy in reduction of cardiovascular events than low potency statins or high-potency statins at low doses.[41] However, patients treated with lipid-lowering medications should be carefully monitored for the development of myositis or liver disease. In addition, statin monotherapy is not recommended for severe or very severe hypertriglyceridemia.[38]

A study by Shimabukuro et al found that the impact on lipoprotein subclass profiles varies between pitavastatin and atorvastatin. Determining the lipoprotein subclass profile and selecting the appropriate statin in patients with diabetes and an additional cardiovascular risk, such as low HDL cholesterol or hypertriglyceridemia may be beneficial.[44, 45, 46, 47]

A patient with a mixed hyperlipidemia and other risk factors for CAD may warrant a niacin-statin or fibric acid–statin combination when the risks versus benefits are considered.

Other considerations

Do not start medications that may cause severe hypertriglyceridemia without first checking baseline triglycerides. These drugs may be used in patients with mildly elevated triglycerides and are not absolutely contraindicated in patients with significantly elevated triglycerides. Patients must be closely monitored, and a triglyceride-lowering medication should be instituted, if necessary.

Ileal bypass surgery and plasmapheresis to lower elevated serum lipids are used in selected cases of familial hypercholesterolemia. Only experienced physicians should use these therapies.

Normally, in patients with acute pancreatitis secondary to severe hypertriglyceridemia, triglyceride levels rapidly decrease, often by 1000 mg/dL each day when treated with standard medical therapy: nothing by mouth (NPO), intravenous (IV) hydration, and if needed, parenteral insulin to reduce plasma glucose levels. If triglyceride levels do not decrease or, more ominously, if they increase, more aggressive intervention with plasmapheresis is probably warranted.

If the primary care provider cannot control a patient's triglycerides, referral should be made to a lipidologist or endocrinologist with expertise in treating severe and difficult-to-manage lipid disorders.[48]

FDA warnings

On March 1, 2012, the US Food and Drug Administration (FDA) issued updates to the prescribing information concerning interactions between protease inhibitors (such as those used to treat hepatitis C or human immunodeficiency virus infection) and certain statin drugs, notably that the combination of these agents taken together may raise the blood levels of statins and increase the risk for myopathy.[49] The most serious form of myopathy, rhabdomyolysis, can damage the kidneys and lead to kidney failure, which can be fatal.[49]

Two days earlier, on February 28, 2012, the FDA approved important safety label changes for statins, including removal of routine monitoring of liver enzymes from drug labels.[50] Information about the potential for generally nonserious and reversible cognitive side effects and reports of increased blood sugar and glycosylated hemoglobin (HbA1c) levels were added to the statin labels. In addition, the lovastatin label was extensively updated with new contraindications and dose limitations when this agent is taken with certain medicines that can increase the risk for myopathy.[50]

On June 8, 2011, the FDA recommended limiting the use of the highest approved dose of simvastatin (Zocor) (80 mg) due to the increased risk of myopathy.[51] The agency also required changes to the simvastatin label to add new contraindications (should not be used with certain medications) and dose limitations for using simvastatin with certain medicines.[51]


Pharmacologic Therapy

High doses of a strong statin (simvastatin, atorvastatin, rosuvastatin) lower triglycerides, by as much as approximately 50%, and raise high-density lipoprotein (HDL) cholesterol.[37] The greater the baseline level of triglycerides the greater the percent triglyceride reduction will be with statin treatment.[52] In addition to statins, 3 classes of medications are appropriate for the management of major triglyceride elevations: fibric acid derivatives, niacin, and omega-3 fatty acids.[37, 42, 52]

Nicotinic acid combined with a statin generally improves low-density lipoprotein (LDL) cholesterol, HDL cholesterol, and triglyceride levels. However, the use of fibric acids has a variable effect on LDL cholesterol despite reducing triglyceride levels and increasing HDL cholesterol levels.[37, 52] In patients with diagnosed coronary artery disease (CAD) at very high risk of recurrent cardiovascular events, it may be necessary to use the combination of a cholesterol-lowering drug with a triglyceride-lowering drug to reach the non-HDL cholesterol goal.[37]


Currently, 4 fibrates are used clinically; 2 are available in the United States, both in generic formulations: gemfibrozil (Lopid) and fenofibrate (multiple brand names). Bezafibrate and ciprofibrate, available in Europe and elsewhere, have not been approved by the US Food and Drug Administration (FDA). A new fenofibrate formulation known as fenofibric acid (Trilipix) has been approved by the FDA with a specific indication for use with a statin in patients with mixed dyslipidemia.[53] No head-to-head trials have been performed, and the older fenofibrate formulation also appears to be safe when combined with a statin. When combined with a statin, gemfibrozil is not as safe as fenofibrate, and if at all possible, fenofibrate should be used in patients treated with a statin.[54]

A review of gemfibrozil, fenofibrate, and bezafibrate described their beneficial lipid effects and the association of these drugs with reductions in coronary morbidity and mortality (although no substantial effect on total mortality was found).[55]

Clinical trials have shown that some fibrates cause reversible increases in serum creatinine levels but either have no impact on or slightly decrease albumin excretion.[56] Moreover, the kidney is the primary route for elimination of most fibrates, and dose reductions are indicated for reduced creatinine clearance. The half-life of gemfibrozil is independent of renal function, and it is the drug of choice for patients with chronic kidney disease.[57]

Fenofibrate has been marketed in the United States under multiple brand names, each with different doses; generic fenofibrate is also available in different doses. In addition, micronized and nonmicronized formulations are produced; whether one formulation has any advantage over the other is not clear.

All manufacturers provide high- and low-dose fenofibrate tablets. The standard adult dose is always more than 100 mg/d; the lower dose is indicated for patients with renal dysfunction (creatinine clearance < 80). Fibrates are contraindicated in patients with creatine clearance of less than 30. The formulation known as fenofibric acid (Trilipix) was approved by the FDA for use with a statin in mixed dyslipidemia.[53, 54, 55, 56, 57] The older fenofibrate formulation also appears to be safe when combined with a statin.


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.[38] Niacin also reliably and significantly lowers LDL cholesterol levels, which the other major triglyceride-lowering medications do not. In the Coronary Drug Project, niacin, in comparison with placebo, reduced coronary events.[58]


Niacin has multiple adverse effects, the worst of which is chemical hepatitis. However, at doses of 1.5-2 g/d, complications are unusual. Sustained-release niacin is more hepatotoxic than immediate-release niacin but is better tolerated.[59] Flushing, itching, and rash are expected adverse effects that are less common with long-acting formulations. These symptoms are an annoyance but are not life threatening and may be minimized by starting at low doses and increasing slowly. Switching from immediate-release niacin to an equal dose of time-release preparation has been reported to cause severe hepatotoxicity. Niacinamide, also called vitamin B-3, has no lipid-lowering effects; nor does inositol hexanicotinate.

If niacin is prescribed for patients with type 2 diabetes, glucose control should be carefully monitored, modest increases in insulin resistance can occur.[60] In addition, because uncontrolled diabetes can cause hypertriglyceridemia, patients with diabetes mellitus should be treated aggressively to reduce the HbA1c level to less than 7%. Niacin is the best available agent to increase HDL cholesterol. It also lowers lipoprotein (a).

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. The triglyceride-lowering impact of fish oils is entirely dependent on the omega-3 content, and, therefore, the number of capsules required for a total dose of 4 g/d requires determining the content of eicosapentaenoic (EPA) and docosahexaenoic (DHA) per capsule. A recent study of nonprescription fish and krill oil capsules available in the United States as dietary supplements showed that the content of DHA ranges from 0.05 to 0.22 mg/g and of EPA from 0.08 to 0.45 mg/g. These dietary supplements do not undergo rigorous clinical trials to prove efficacy or safety, nor are they FDA approved to treat or prevent disease. the labels of the most common fish oil supplement capsules in the United States claim to provide 180 mg of EPAand 120 mg ofDHA per capsule. Therefore, a minimum dose of 4 g of omega-3 fatty acids per day may require at least 8-12 capsules.[61]

Low doses of EPA and DHA (750-1000 mg/d) that do not affect lipid levels have been demonstrated to lower the incidence of fatal coronary events, probably due primarily to its antiarrhythmic properties.[62]

Several prescription fish oil capsules have been approved by the FDA to treat triglyceride levels of more than 500 mg/dL. One example is Lovaza. One 1-g capsule contains at least 900 mg of ethyl esters of omega-3 fatty acids (~465 mg of EPA and 375 mg of DHA). High-dose omega-3 products containing DHA increase LDL cholesterol levels; the impact on HDL cholesterol levels varies.

Another prescription fish oil is an ultra-pure omega fatty acid that contains an ethyl ester of EPA, icosapent ethyl (Vascepa). Each 1-g icosapent capsule contains at least 96% EPA and no DHA. Past studies suggest that highly purified EPA may lower triglyceride (TG) levels without increasing LDL cholesterol levels.[63, 64] 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).

The Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension (MARINE) trial randomized 229 diet-stable patients with fasting TG levels from 500-2000 mg/dL (with or without background statin therapy) to icosapent 4 g/day, icosapent 2 g/day, or placebo. Results showed that icosapent significantly reduced the TG levels and improved other lipid parameters without significantly increasing the LDL cholesterol levels. Icosapent 4 g/day reduced the placebo-corrected TG levels by 33.1% (n = 76; P < 0.0001) and icosapent 2 g/day by 19.7% (n = 73; P = 0.0051). For a baseline TG level >750 mg/dL, icosapent 4 g/day reduced the placebo-corrected TG levels by 45.4% (n = 28; P = 0.0001) and icosapent 2 g/day by 32.9% (n = 28; P = 0.0016).[65]

An omega-3 carboxylic acid product (Epanova) was approved by the FDA in May 2014. It is the first prescription omega-3 product in free fatty acid form. It is indicated as an adjunct to diet to reduce triglyceride levels in adults with severe hypertriglyceridemia (TGs ≥500 mg/dL).

Approval was based on data from the Phase III EVOLVE (EpanoVa fOr Lowering Very High triglyceridEs) trial. The trial showed a significant decrease in non-HCL-C, ratio of total cholesterol to HDL-C, VLDLs, Apo-C, phospholipase A2, and arachidonic acid with omega-3 carboxylic acids over a 12-week period compared with olive oil in patients with TGs ≥500 mg/dL.[66]

HMG-CoA reductase inhibitors (statins)

For patients with mixed hyperlipidemias (elevations of both LDL cholesterol and triglycerides), a moderate dose of a hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor may be appropriate if the amount of triglyceride lowering necessary is only about 20%. Maximum doses of the strongest statins, atorvastatin, simvastatin, and rosuvastatin, lower triglycerides approximately 40%, but such doses are not appropriate first-line therapy unless triglycerides are less than 500 mg/dL and LDL-C is elevated.[38, 67]

It is recommended that patients intolerant to one statin (eg, owing to myalgias) try the other statins before excluding the entire class, particularly in secondary prevention of dyslipidemias.[37] If the patients cannot take statins other agents suitable for management of mixed dyslipidemia may be tried, either alone or in combination therapy, including niacin, fibric acids, and ezetimibe.[37] Bile acid sequestrants can raise triglycerides and are contraindicated in patients with very high triglycerides.[52]

Note the following[37] :

  • Statins are more effective when taken at bedtime or in the evening
  • Although lovastatin should be taken with food to maximize its absorption, the sustained-release formulation should be taken on an empty stomach
  • A major reduction in HDL may occur in some patients on combined therapy with fibrates and thiazolidinediones (check HDL levels 1-2 mo following initiation of this combination therapy)
  • Do not adjust dosing regimens more often than every 4 weeks after a fasting lipid panel has been obtained

Other agents

Bile acid sequestrants (cholestyramine or colestipol) raise triglyceride levels and are not appropriate therapy for hypertriglyceridemia. However, in patients with a mixed hyperlipidemia, resins may be combined with niacin or a fibrate.

Patients with the metabolic syndrome are often treated with metformin, which improves impaired fasting glucose levels, frequently causes modest weight loss, and can lower triglyceride levels.

Ezetimibe (Zetia) is a selective cholesterol-absorption inhibitor that has been used as secondary therapy in the management of dyslipidemia, such as in the following clinical situations[37] :

  • High LDL, low HDL (< 40 mg/dL), and high triglycerides (>200 mg/dL)
  • High LDL, regardless of whether the HDL level is lower than 40 mg/dL or not

Adult Treatment Panel Guidelines

The Adult Treatment Panel guidelines (ATP III) were published in 2001 and reclassified serum triglycerides (TG) as shown in Table 2, below. The update to the ATP III guidelines (ATP IV)is still in progress as of autumn 2012, according to the National Heart, Lung, and Blood Institute Website.

Table 2. Classification of Triglycerides (Open Table in a new window)

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]

If triglycerides are 500 or above, their treatment takes priority over low-density lipoprotein (LDL) treatment to prevent pancreatitis, unless the patient has a high risk for an acute coronary artery disease (CAD) event, in which case simultaneous treatment for both conditions should be considered.

If the secondary conditions that raise triglyceride levels cannot be managed successfully and if triglycerides are 200-499 mg/dL, the non–high-density lipoprotein (HDL) cholesterol (total cholesterol – HDL) can be used as the initial target of using LDL-lowering medication (see Table 3, below). The non–HDL cholesterol is the sum of the cholesterol carried by the atherogenic lipoproteins, LDL, very low-density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL). The goals for non–HDL levels, similar to those for LDL levels, are dependent on risk and are 30 mg/dL higher than the corresponding LDL goals.

Table 3. Classification of LDL Cholesterol and Non-HDL Cholesterol (Open Table in a new window)

Classification LDL Goal,


Non-HDL Goal,


CHD and CHD risk equivalent, diabetes mellitus, and the following: 10-year risk for CHD >20% < 100 < 130
Two or more risk factors and the following: 10-year risk < 20% < 130 < 160
0-1 risk factor < 160 < 190
CHD = coronary heart disease; LDL = low-density lipoprotein; HDL = high-density lipoprotein.

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]

When hypertriglyceridemia is diagnosed, secondary causes should be sought out and controlled. If the triglyceride level is below 500 mg/dL, triglyceride-lowering medication may be withheld while secondary causes are managed. For example, lowering a substantially elevated HbA1c may normalize the triglycerides; or at least facilitate their treatment.


Diet and Exercise

The importance of obesity, a sedentary lifestyle, very high fat diet, and intake of large concentrations of refined carbohydrates should not be underestimated as causes of severe hypertriglyceridemia. A dietitian or knowledgeable physician should counsel the patient. Instituting a program of progressive aerobic and toning exercise, weight loss, and dietary management can significantly lower triglyceride levels and, in some cases, normalize them.

It is recommended that individuals consume less than 20% of calories as fat, with saturated fat reduced to less than 7% of calories, which may be achieved by avoiding trans fats, limiting dietary cholesterol to less than 200 mg/d.[37] Restrict refined carbohydrates, particularly sugar and liquid calories. In addition, lowering low-density lipoprotein (LDL) may be enhanced by adding dietary options such as 2 g/d of plant stanols/sterols and at least 5-10 g/d of viscous soluble fiber to the diet.[37]

Alcohol consumption should also be severely limited or abstained; consuming more than 1 standard alcoholic drink per day may worsen hypertriglyceridemia. In March 2011, the American Dietetic Association published updated evidence-based guidelines for nutrition practice for disorders of lipid metabolism.

Total fat intake

Total fat intake should be restricted if this intervention assists in weight loss. If triglyceride levels are greater than 1000 mg/dL, allowing no more than 10% of total calories from fat will usually lower triglycerides promptly and dramatically.

Fat restriction is a 2-edged sword. Reducing fat intake causes needed weight loss, and triglycerides usually improve. When triglycerides are severely elevated (>1000 mg/dL), suggesting impaired or absent lipoprotein lipase activity, a low-fat diet decreases chylomicron and very low-density lipoprotein (VLDL) production and improves the metabolism of these triglyceride-rich lipoproteins.

However, in the setting of stable weight and moderately elevated triglycerides, a very low-fat diet increases triglycerides and may, in addition, decrease high-density lipoprotein (HDL) levels. Patients who are extremely compliant and motivated may choose to follow such a diet in the hope of improving their cholesterol levels. If they have a mixed hyperlipidemia, their LDL level certainly will decrease. However, such a diet will, if anything, cause further deterioration in the HDL and triglyceride levels. If the patient has an isolated triglyceride elevation and does not lose weight on the diet, the triglyceride levels may increase. In such cases, addition of a healthy fat (monounsaturated or polyunsaturated fat) lowers levels of triglycerides, increases HDL, and sometimes decreases LDL.

Carbohydrate intake

In cases in which dietary intake of sugar and white flour products is substantial, restricting simple carbohydrates and increasing dietary fiber are important adjuncts that can lower triglycerides substantially. Large quantities or fruit juice or nondiet soda can increase triglycerides dramatically.

Again, alcohol should be eliminated or restricted to no more than 1 standard alcoholic beverage per day.

Omega-3 (N-3) fatty acids

The class of polyunsaturated fats known as omega-3 fatty acids, which are derived mainly from fatty fish and some plant products (flax seed), has a unique impact on triglycerides. In large amounts (10 or more g/d), N-3 fatty acids lower triglycerides 40% or more.

To achieve this dose, purified capsules are usually necessary, but some patients may prefer to eat large quantities of fatty fish. The fish highest in N-3 fatty acids are sardines, herring, and mackerel; daily servings of 1 pound or more may be necessary. If weight gain ensues, triglyceride lowering will be compromised.


Exercise, particularly sustained aerobic activity, can have a dramatic impact on triglyceride levels and may increase HDL slightly. If patients have no known cardiovascular disease, they should be encouraged to begin an exercise program of graduated aerobics and toning.

The American Heart Association (AHA) recommends 30-60 minutes of aerobic exercise most days of the week and toning for 20-30 minutes twice a week. Frequent and sustained exercise lowers elevated triglyceride levels and may raise HDL cholesterol levels.

Before beginning an exercise program, consider giving a stress test to older patients and patients with multiple risk factors for coronary artery disease, as these patients are at increased risk for cardiovascular disease.

Exercise prescription also has substantial benefits beyond lipid effects as follows:

  • Reduced weight
  • Decreased insulin resistance
  • Decreased blood pressure
  • Improved cardiovascular conditioning

Overall reduction in acute cardiovascular events is also a likely benefit of regular exercise. Toning of large muscles groups (abdomen, back, legs, arms) also improves metabolism of triglyceride-rich lipoproteins and lowers triglycerides.


Pregnant Patients

Women with elevated triglycerides before conception may develop severe hypertriglyceridemia, with triglyceride levels well above 1000 mg/dL, and the concomitant risk of pancreatitis. These women should be counseled regarding diet, exercise, and weight management before becoming pregnant and must be monitored closely during their pregnancies.[68] All pregnancies require occasional triglyceride monitoring. Simple inspection to rule out lipemic serum is all that is necessary.

The use of lipid-lowering drugs in pregnant patients and pediatric patients has not been thoroughly investigated. Thus, most of the medications to treat hypertriglyceridemia are contraindicated during pregnancy, although treatment with gemfibrozil in a patient with severe hypertriglyceridemia and pancreatitis has been reported.[68] Omega-3 fatty acids may be a more acceptable intervention, but the safety of high-dose N-3 fatty acids has not been proven.


Screening and Prevention

To decrease the risk of cardiovascular disease, patients should avoid smoking, obesity, and sedentary lifestyles. Moreover, pursue aggressive treatment of hypertension and diabetes.

Primary and secondary prevention

Patients with hypertriglyceridemia, particularly if the high-density lipoprotein (HDL) level is low, are at risk for cardiovascular events. For primary prevention, it is recommended that men aged 35 and older—and those aged 20-35 if they are at increased risk—are screened for coronary heart disease (CHD) with a fasting lipid profile; screening for women is recommended only for those at increased risk for CHD.[41, 31] For patients who were screened with a nonfasting due to patient convenience, follow-up on abnormal nonfasting lipid levels with a fasting lipid profile. Screening should be repeated every 5 years in patients with normal lipid levels.[41]

In secondary prevention, all patients with CHD, other atherosclerotic cardiovascular disease (ASCVD), diabetes mellitus, or a Framingham 10-year risk of greater than 20% should be screened with a full lipid panel.[41] Evaluate the patient’s risk for cardiovascular events. Patients considered at high risk include those who have CHD without major risk factors or other risks associated with very high risk.

Patients considered at very high risk include individuals with CHD or other atherosclerotic vascular disease as well as 1 or more of the following: major risk factors (eg, diabetes, hypertension, metabolic syndrome, active cigarette smoking) or acute coronary syndrome.[41, 43] Thus, these patients should be treated not only for their lipid disorder but also for other modifiable cardiovascular risk factors, such as hypertension, diabetes, smoking, sedentary lifestyle, and obesity.[69, 70]

The Endocrine Society’s 2012 guidelines in evaluating and treating hypertriglyceridemia included screening adults for this condition as part of a lipid panel at least at 5-year intervals.[38] For pediatric patients with dyslipidemia, the American Association of Clinical Endocrinologists (AACE) recommends early diagnosis and management to reduce LDL levels, thereby reducing the risk for cardiovascular events in adulthood.[62]

Diet and exercise

Although the rare inherited disorders of severe hypertriglyceridemia require heroic restrictions in dietary fat, most elevated triglycerides can be controlled, at least partially, by a program of diet, exercise, and weight loss. Lifestyle modification can be more effective than a triglyceride-lowering medication if the habits are in need of intervention and the patient is willing and able to make significant changes. Therefore, prevention entails pursuing an active lifestyle with regular aerobic and toning exercise; adhering to a diet low in simple carbohydrates and alcohol and, if the triglycerides are well above 1000 mg/dL, low in fat; and maintaining a lean body habitus. These habits have the added benefit of reducing the probability of developing type 2 diabetes mellitus and hypertension.

Patients with modest triglyceride elevations may develop severe hypertriglyceridemia and risk of pancreatitis if an aggravating agent is instituted. Drugs such as oral isotretinoin and unopposed oral estrogen replacement therapy should be used with caution.

During pregnancy, severe hypertriglyceridemia is an unusual complication and may cause pancreatitis. Many case reports have been published describing interventions to manage this condition. Most commonly, a very low-fat diet was sufficient to control triglycerides and prevent pancreatitis. Intermittent and, in persistent cases, continuous total parenteral nutrition has been used—usually in the third trimester. Reports also have been published describing plasma exchange or apheresis, as well as early third-trimester termination of pregnancy by cesarean section.



A specialist in lipid disorders may be helpful in treating the hyperlipidemia that develops in patients, which can be very severe and difficult to treat, often requiring multiple lipid-lowering agents.

In addition, patients should receive nutrition counseling and should be advised to restrict calories if they are overweight. These individuals also should reduce saturated and trans fats and cholesterol intake.


Long-Term Monitoring

Follow up with patients who are on diet and lipid-lowering therapy. Periodically monitor their blood cholesterol, triglyceride, and lipoprotein levels. If patients are taking lipid-lowering medications, obtain periodic liver function tests.

If patients are taking fibric acid derivatives or statins, advise them to report unexplained generalized muscle pain, tenderness, or weakness. Perform creatinine kinase determinations in these individuals.

In patients with diabetes, aggressive glucose control should be pursued with diet, oral hypoglycemic agents, or insulin.

Contributor Information and Disclosures

Mary Ellen T Sweeney, MD Associate Professor of Medicine (Endocrinology, Diabetes, and Metabolism), Department of Medicine, Emory University School of Medicine; Physician, Division of Endocrinology, Veterans Administration Medical Center; Physician, Lipid Metabolism Clinic, Emory Healthcare, The Emory Clinic

Mary Ellen T Sweeney, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, National Lipid Association

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.


Steve Charles, MD Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine; Adjunct Professor of Ophthalmology, Columbia College of Physicians and Surgeons; Clinical Professor Ophthalmology, Chinese University of Hong Kong

Steve Charles, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Club Jules Gonin, Macula Society, and Retina Society

Disclosure: Alcon Laboratories Consulting fee Consulting; OptiMedica Ownership interest Other; Topcon Medical Lasers Consulting fee Consulting

Karen E Friday, MD, FACP Clinical Core Director of Tulane Xavier National Center of Excellence, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Tulane University School of Medicine

Karen E Friday, MD, FACP is a member of the following medical societies: American College of Physicians, American Diabetes Association, American Heart Association, American Society for Clinical Nutrition, and Endocrine Society

Disclosure: AstraZeneca own AstraZeneca stock None; Merck own Merck stock None; Schering Plough own Schering Plough stock None; Medco Health own Medco Health stock None

Robert A Gabbay, MD, PhD Associate Professor of Medicine, Division of Endocrinology, Diabetes and Metabolism, Laurence M Demers Career Development Professor, Penn State College of Medicine; Director, Diabetes Program, Penn State Milton S Hershey Medical Center; Executive Director, Penn State Institute for Diabetes and Obesity

Robert A Gabbay, MD, PhD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association, and Endocrine Society

Disclosure: Novo Nordisk Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching

Steven R Gambert, MD Professor of Medicine, Johns Hopkins University School of Medicine; Director of Geriatric Medicine, University of Maryland Medical Center and R. Adams Cowley Shock Trauma Center

Steven R Gambert, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American Geriatrics Society, Association of Professors of Medicine, Endocrine Society, and Gerontological Society of America

Disclosure: Nothing to disclose.

Romesh Khardori, MD, PhD Professor and Director, Division of Endocrinology, Metabolism, and Molecular Medicine, Southern Illinois University School of Medicine

Romesh Khardori, MD, PhD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society of Andrology, Endocrine Society, and Illinois State Medical Society

Disclosure: Nothing to disclose.

Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

  1. Nainggolan L. FDA Approves Epanova for Severe Hypertriglyceridemia. Medscape Medical News. Available at Accessed: May 12, 2014.

  2. Wu CW, Lin PY, Liu YF, Liu TC, Lin MW, Chen WM, et al. Central corneal mosaic opacities in Schnyder's crystalline dystrophy. Ophthalmology. 2005 Apr. 112(4):650-3. [Medline].


  4. Mahley RW, Rall SC Jr. Type III hyperlipoproteinemia (dysbetalipoproteinemia): the role of apolipoprotein E in normal and abnormal metabolism. Scriver CR, Beaudet AR, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001. 2835-62.

  5. Kane JP. Structure and function of the plasma lipoproteins and their receptors. Fuster V, Ross R, Topol EJ, eds. Atherosclerosis and Coronary Artery Disease. Philadelphia, Pa: Lippincott-Raven; 89-103. 1996: .

  6. Mahley RW, Huang Y, Rall SC Jr. Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia). Questions, quandaries, and paradoxes. J Lipid Res. 1999 Nov. 40(11):1933-49. [Medline].

  7. Smelt AH, de Beer F. Apolipoprotein E and familial dysbetalipoproteinemia: clinical, biochemical, and genetic aspects. Semin Vasc Med. 2004 Aug. 4(3):249-57. [Medline].

  8. Huang Y, Schwendner SW, Rall SC Jr, Sanan DA, Mahley RW. Apolipoprotein E2 transgenic rabbits. Modulation of the type III hyperlipoproteinemic phenotype by estrogen and occurrence of spontaneous atherosclerosis. J Biol Chem. 1997 Sep 5. 272(36):22685-94. [Medline].

  9. Zhang SH, Reddick RL, Piedrahita JA, Maeda N. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science. 1992 Oct 16. 258(5081):468-71. [Medline].

  10. Corbo RM, Scacchi R. Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a 'thrifty' allele?. Ann Hum Genet. 1999 Jul. 63:301-10. [Medline].

  11. Feussner G, Piesch S, Dobmeyer J, Fischer C. Genetics of type III hyperlipoproteinemia. Genet Epidemiol. 1997. 14(3):283-97. [Medline].

  12. Davignon J, Gregg RE, Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis. 1988 Jan-Feb. 8(1):1-21. [Medline].

  13. Hassing HC, Surendran RP, Mooij HL, Stroes ES, Nieuwdorp M, Dallinga-Thie GM. Pathophysiology of hypertriglyceridemia. Biochim Biophys Acta. 2012 May. 1821(5):826-32. [Medline].

  14. 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. 2001 May 16. 285(19):2486-97. [Medline].

  15. Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011 May 24. 123(20):2292-333. [Medline].

  16. Pajukanta P, Porkka KV. Genetics of familial combined hyperlipidemia. Curr Atheroscler Rep. 1999 Jul. 1(1):79-86. [Medline].

  17. Kolovou GD, Anagnostopoulou KK, Kostakou PM, Bilianou H, Mikhailidis DP. Primary and secondary hypertriglyceridaemia. Curr Drug Targets. 2009 Apr. 10(4):336-43. [Medline].

  18. Pilia G, Chen WM, Scuteri A, Orrú M, Albai G, Dei M, et al. Heritability of cardiovascular and personality traits in 6,148 Sardinians. PLoS Genet. 2006 Aug 25. 2(8):e132. [Medline]. [Full Text].

  19. Willer CJ, Mohlke KL. Finding genes and variants for lipid levels after genome-wide association analysis. Curr Opin Lipidol. 2012 Apr. 23(2):98-103. [Medline]. [Full Text].

  20. Johansen CT, Wang J, Lanktree MB, Cao H, McIntyre AD, Ban MR, et al. Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia. Nat Genet. 2010 Aug. 42(8):684-7. [Medline]. [Full Text].

  21. Kathiresan S, Willer CJ, Peloso GM, Demissie S, Musunuru K, Schadt EE, et al. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet. 2009 Jan. 41(1):56-65. [Medline]. [Full Text].

  22. Hiramatsu M, Oguri M, Kato K, Horibe H, Fujimaki T, Watanabe S, et al. Synergistic effects of genetic variants of APOA5 and BTN2A1 on dyslipidemia or metabolic syndrome. Int J Mol Med. 2012 Jul. 30(1):185-92. [Medline].

  23. Shen GQ, Li L, Wang QK. Genetic variant R952Q in LRP8 is associated with increased plasma triglyceride levels in patients with early-onset CAD and MI. Ann Hum Genet. 2012 May. 76(3):193-9. [Medline].

  24. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002 Jan 16. 287(3):356-9. [Medline].

  25. Sumner AE, Cowie CC. Ethnic differences in the ability of triglyceride levels to identify insulin resistance. Atherosclerosis. 2008 Feb. 196(2):696-703. [Medline].

  26. Assmann G, Schulte H. Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (the PROCAM experience). Prospective Cardiovascular Münster study. Am J Cardiol. 1992 Sep 15. 70(7):733-7. [Medline].

  27. Stamler J, Wentworth D, Neaton JD. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA. 1986 Nov 28. 256(20):2823-8. [Medline].

  28. Athyros VG, Giouleme OI, Nikolaidis NL, Vasiliadis TV, Bouloukos VI, Kontopoulos AG, et al. Long-term follow-up of patients with acute hypertriglyceridemia-induced pancreatitis. J Clin Gastroenterol. 2002 Apr. 34(4):472-5. [Medline].

  29. Brunzell JD, Bierman EL. Chylomicronemia syndrome. Interaction of genetic and acquired hypertriglyceridemia. Med Clin North Am. 1982 Mar. 66(2):455-68. [Medline].

  30. Chait A, Brunzell JD. Chylomicronemia syndrome. Adv Intern Med. 1992. 37:249-73. [Medline].

  31. US Preventive Services Task Force. Screening for lipid disorders in adults: U.S. Preventive Services Task Force recommendation statement. Rockville, Md: Agency for Healthcare Research and Quality; 2008.

  32. Jellinger PS, Smith DA, Mehta AE, Ganda O, Handelsman Y, Rodbard HW, et al. American Association of Clinical Endocrinologists' Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis. Endocr Pract. 2012 Mar-Apr. 18 Suppl 1:1-78. [Medline].

  33. Fortson MR, Freedman SN, Webster PD 3rd. Clinical assessment of hyperlipidemic pancreatitis. Am J Gastroenterol. 1995 Dec. 90(12):2134-9. [Medline].

  34. Leaf DA. Chylomicronemia and the chylomicronemia syndrome: a practical approach to management. Am J Med. 2008 Jan. 121(1):10-2. [Medline].

  35. Pandhi D, Gupta P, Singal A, Tondon A, Sharma S, Madhu SV. Xanthelasma palpebrarum: a marker of premature atherosclerosis (risk of atherosclerosis in xanthelasma). Postgrad Med J. 2012 Apr. 88(1038):198-204. [Medline].

  36. Rohrich RJ, Janis JE, Pownell PH. Xanthelasma palpebrarum: a review and current management principles. Plast Reconstr Surg. 2002 Oct. 110(5):1310-4. [Medline].

  37. Institute for Clinical Systems Improvement. Lipid management in adults. Bloomington, Minn: Institute for Clinical Systems Improvement; 2009.

  38. Berglund L, Brunzell JD, Goldberg AC, Goldberg IJ, Sacks F, Murad MH, et al. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012 Sep. 97(9):2969-89. [Medline]. [Full Text].

  39. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA. 2007 Jul 18. 298(3):309-16. [Medline].

  40. Haffner SM. Secondary prevention of coronary heart disease: the role of fibric acids. Circulation. 2000 Jul 4. 102(1):2-4. [Medline].

  41. University of Michigan Health System. Screening and management of lipids. Ann Arbor, Mich: University of Michigan Health System; 2009.

  42. Klop B, Wouter Jukema J, Rabelink TJ, Castro Cabezas M. A physician's guide for the management of hypertriglyceridemia: the etiology of hypertriglyceridemia determines treatment strategy. Panminerva Med. 2012 Jun. 54(2):91-103. [Medline].

  43. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, et al. A summary of implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Arterioscler Thromb Vasc Biol. 2004 Aug. 24(8):1329-30. [Medline].

  44. Shimabukuro M, Higa M, Tanaka H, Shimabukuro T, Yamakawa K, Masuzaki H. Distinct effects of pitavastatin and atorvastatin on lipoprotein subclasses in patients with Type 2 diabetes mellitus. Diabet Med. 2011 Jul. 28(7):856-64. [Medline].

  45. Hadfield SG, Horara S, Starr BJ, Yazdgerdi S, Marks D, Bhatnagar D, et al. Family tracing to identify patients with familial hypercholesterolaemia: the second audit of the Department of Health Familial Hypercholesterolaemia Cascade Testing Project. Ann Clin Biochem. 2009 Jan. 46:24-32. [Medline].

  46. Versmissen J, Oosterveer DM, Yazdanpanah M, Defesche JC, Basart DC, Liem AH, et al. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ. 2008 Nov 11. 337:a2423. [Medline]. [Full Text].

  47. van der Graaf A, Cuffie-Jackson C, Vissers MN, Trip MD, Gagné C, Shi G, et al. Efficacy and safety of coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia. J Am Coll Cardiol. 2008 Oct 21. 52(17):1421-9. [Medline].

  48. Schaap-Fogler M, Schurr D, Schaap T, Leitersdorf E, Rund D. Long-term plasma exchange for severe refractory hypertriglyceridemia: a decade of experience demonstrates safety and efficacy. J Clin Apher. 2009. 24(6):254-8. [Medline].

  49. US Food and Drug Administration. Safety: statins and HIV or hepatitis C drugs: drug safety communication - interaction increases risk of muscle injury. Posted: March 1, 2012. Available at Accessed: November 1, 2013.

  50. US Food and Drug Administration. Safety: statin drugs - drug safety. Available at Accessed: November 1, 2013.

  51. US Food and Drug Administration. Safety: Zocor (simvastatin): label change - new restrictions, contraindications, and dose limitations. Posted: June 8, 2011. Available at Accessed: November 1, 2013.

  52. Maki KC, Bays HE, Dicklin MR. Treatment options for the management of hypertriglyceridemia: strategies based on the best-available evidence. J Clin Lipidol. 2012 Sep-Oct. 6(5):413-26. [Medline].

  53. Mohiuddin SM, Pepine CJ, Kelly MT, Buttler SM, Setze CM, Sleep DJ, et al. Efficacy and safety of ABT-335 (fenofibric acid) in combination with simvastatin in patients with mixed dyslipidemia: a phase 3, randomized, controlled study. Am Heart J. 2009 Jan. 157(1):195-203. [Medline].

  54. Wu J, Song Y, Li H, Chen J. Rhabdomyolysis associated with fibrate therapy: review of 76 published cases and a new case report. Eur J Clin Pharmacol. 2009 Dec. 65(12):1169-74. [Medline].

  55. Abourbih S, Filion KB, Joseph L, Schiffrin EL, Rinfret S, Poirier P, et al. Effect of fibrates on lipid profiles and cardiovascular outcomes: a systematic review. Am J Med. 2009 Oct. 122(10):962.e1-8. [Medline].

  56. Sica DA. Fibrate therapy and renal function. Curr Atheroscler Rep. 2009 Sep. 11(5):338-42. [Medline].

  57. Harper CR, Jacobson TA. Managing dyslipidemia in chronic kidney disease. J Am Coll Cardiol. 2008 Jun 24. 51(25):2375-84. [Medline].

  58. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986 Dec. 8(6):1245-55. [Medline].

  59. McKenney JM, McCormick LS, Weiss S, Koren M, Kafonek S, Black DM. A randomized trial of the effects of atorvastatin and niacin in patients with combined hyperlipidemia or isolated hypertriglyceridemia. Collaborative Atorvastatin Study Group. Am J Med. 1998 Feb. 104(2):137-43. [Medline].

  60. Goldberg RB, Jacobson TA. Effects of niacin on glucose control in patients with dyslipidemia. Mayo Clin Proc. 2008 Apr. 83(4):470-8. [Medline].

  61. Roth EM, Bays HE, Forker AD, Maki KC, Carter R, Doyle RT, et al. Prescription omega-3 fatty acid as an adjunct to fenofibrate therapy in hypertriglyceridemic subjects. J Cardiovasc Pharmacol. 2009 Sep. 54(3):196-203. [Medline].

  62. Lavie CJ, Milani RV, Mehra MR, Ventura HO. Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J Am Coll Cardiol. 2009 Aug 11. 54(7):585-94. [Medline].

  63. Egert S, Kannenberg F, Somoza V, Erbersdobler HF, Wahrburg U. Dietary alpha-linolenic acid, EPA, and DHA have differential effects on LDL fatty acid composition but similar effects on serum lipid profiles in normolipidemic humans. J Nutr 2009;139:861-68.

  64. Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J. Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. Atherosclerosis 2006;189:19-30.

  65. Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN. Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial). Am J Cardiol. 2011 Sep 1. 108(5):682-90. [Medline].

  66. Kastelein JJ, Maki KC, Susekov A, Ezhov M, Nordestgaard BG, Machielse BN, et al. Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: the EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial. J Clin Lipidol. 2014 Jan-Feb. 8(1):94-106. [Medline].

  67. Fletcher B, Berra K, Ades P, Braun LT, Burke LE, Durstine JL, et al. Managing abnormal blood lipids: a collaborative approach. Circulation. 2005 Nov 15. 112(20):3184-209. [Medline].

  68. Hsia SH, Connelly PW, Hegele RA. Successful outcome in severe pregnancy-associated hyperlipemia: a case report and literature review. Am J Med Sci. 1995 Apr. 309(4):213-8. [Medline].

  69. Kuklina EV, Yoon PW, Keenan NL. Trends in high levels of low-density lipoprotein cholesterol in the United States, 1999-2006. JAMA. 2009 Nov 18. 302(19):2104-10. [Medline].

  70. Hudgins LC, Kleinman B, Scheuer A, White S, Gordon BR. Long-term safety and efficacy of low-density lipoprotein apheresis in childhood for homozygous familial hypercholesterolemia. Am J Cardiol. 2008 Nov 1. 102(9):1199-204. [Medline].

  71. Foran SE, Flood JG, Lewandrowski KB. Measurement of mercury levels in concentrated over-the-counter fish oil preparations: is fish oil healthier than fish?. Arch Pathol Lab Med. 2003 Dec. 127(12):1603-5. [Medline].

  72. Pharmacist's Letter. 2010; 26(1): 260101. Available at Accessed: October 11, 2013.

  73. Pharmacist's Letter. 2012; 28(6): 280606. Available at Accessed: October 11, 2013.

Eruptive xanthomas on the back of a patient admitted with a triglyceride level of 4600 mg/dL and acute pancreatitis.
Close-up of eruptive xanthomas.
Composition of triglyceride (TG)-rich lipoproteins. IDL = intermediate-density lipoprotein; VLDL = very low-density lipoprotein.
Lipoprotein lipase (LPL) releases free fatty acids (FFAs) from chylomicrons (chylo) and produces chylomicron remnants that are small enough to take part in the atherosclerotic process. Chol = cholesterol; TGs, TGS = triglycerides.
Once very low-density lipoprotein (VLDL) has been metabolized by lipoprotein lipase, VLDL remnants in the form of intermediate-density lipoprotein (IDL) can be metabolized by hepatic lipase, producing low-density lipoprotein (LDL), or they can be taken up by the LDL receptor via either apolipoprotein B (apo B) or apo E. Chol = cholesterol; TGs = triglycerides.
Table 1. Fredrickson Classification of Hyperlipidemia
Type Serum Elevation Lipoprotein Elevation
I Cholesterol and triglycerides Chylomicrons
IIa Cholesterol LDL
IIb Cholesterol and triglycerides LDL, VLDL
III Cholesterol and triglycerides IDL
IV Triglycerides VLDL
V Cholesterol and triglycerides VLDL, chylomicrons
IDL = intermediate-density lipoprotein; LDL = low-density lipoprotein; VLDL = very low-density lipoprotein.

Source:  Fredrickson DS, Lees RS. A system for phenotyping hyperlipidaemia. Circulation. Mar 1965;31:321-7.[3]

Table 2. Classification of Triglycerides
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]
Table 3. Classification of LDL Cholesterol and Non-HDL Cholesterol
Classification LDL Goal,


Non-HDL Goal,


CHD and CHD risk equivalent, diabetes mellitus, and the following: 10-year risk for CHD >20% < 100 < 130
Two or more risk factors and the following: 10-year risk < 20% < 130 < 160
0-1 risk factor < 160 < 190
CHD = coronary heart disease; LDL = low-density lipoprotein; HDL = high-density lipoprotein.

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]

Table 4. Fibric Acid Agents, Omega Acid Ethyl Esters, and Niacin Drug Characteristics [72]
Drug Lipid Effects Lipid Effects in Combination with Statin Outcomes Data Comments
Bezafibrate LDL decrease: 9.6-25% (400 mg)

HDL increase: 15-24% (400 mg)

Triglyceride decrease: 25-43% (400 mg)

Further LDL decrease: 1.1% (400 mg)

Further HDL increase: 22% (400 mg)

Further triglyceride decrease: 31.7% (400 mg)

Secondary prevention: Prevents composite endpoint of MI and sudden death in a subgroup with triglycerides of 200 mg/dL or higher. No increase in non-CV death First-line option for triglyceride >10 mmol/L

Option for triglyceride 5-10 mmol/L

Option for low HDL

Reversible increase in serum creatinine

Requires renal dose adjustment

Limited data with statins

Ezetimibe LDL decrease: 18% (10 mg/day)

HDL increase: 1% (10 mg/day)

Triglyceride decrease: 8%

Further LDL decrease: 25%, as add-on

Further HDL increase: 3%, as add-on

Further triglyceride decrease: 14%, as add-on

Prevention of CV events in post-acute coronary syndrome patient when added to statin showed a benefit of reducing the primary endpoint (composite of CV death, MI, unstable angina requiring rehospitalization, coronary revascularization or stroke) by 6.4% vs statin alone

In intermediate outcomes studies, ezetimibe did not reduce regression of carotid intima-media thickness (surrogate marker) when added to a statin

Efficacy studied in combination with atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin

Role as statin add-on to reduce LDL if HDL and triglyceride satisfactory

Fenofibrate LDL decrease: 20.6% (145 mg)

HDL increase: 11% (145 mg)

Triglyceride decrease: 23.5-50.6% (greatest drop in patients with highest triglycerides) (145 mg)

Further LDL decrease: 0-6% (200 mg)

Further HDL increase: 13-17% (200 mg)

Further triglyceride decrease: 20-32% (200 mg)

Prevention of CV events in type 2 diabetes: Did not reduce primary composite outcome (nonfatal MI or CV death). Improved outcomes included nonfatal MI (24% decrease), coronary revascularization (21% decrease), progression to albuminuria, and reduced laser treatments for retinopathy. Nonsignificant increase in risk of CV death.

As statin add-on, did not lower risk of non-fatal MI, nonfatal stroke, or CV death more than statin alone in patients with type 2 diabetes at high risk for CV disease

First-line option for triglyceride >10 mmol/L (about 1000 mg/dL)

Option for triglyceride >500 mg/dL or 5-10 mmol/L

Option for low HDL

Preferred over gemfibrozil for use with statins

Requires renal dose adjustment

Associated with reversible increase in serum creatinine

Gemfibrozil LDL: No effect

HDL increase: 6% (1200 mg/day)

Triglyceride decrease: 33-50% (greatest drop in patients with highest triglycerides) (1200 mg/day)

Further triglyceride decrease: 41%

Further HDL increase: 9%

Primary prevention of coronary heart disease

Secondary prevention of cardiac events in men with low HDL

First-line option for triglyceride >10 mmol/L (about 1000 mg/dL)

Option for triglyceride >500 mg/dL or 5-10 mmol/L

Option for low HDL

Requires renal dose adjustment

Avoid with statin

Icosapent ethyl LDL decrease: 5%

HDL decrease: 4%

Triglyceride decrease: 27%

Further triglyceride decrease: 21.5% (4 g/day), 10.1% (2 g/day)

Further LDL decrease: 6.2% (4 g/day)

A study, REDUCE IT, is underway to look at reduction in CV events with icosapent ethyl Option for triglyceride >500 mg/dL

Safe for use with statins

Use caution with fish or shellfish allergy

Niacin LDL decrease: 14-17% (Niaspan 2 g/day); 12% (niacin immediate-release 1.5 g/day and Niaspan 1.5 g/day)

HDL increase: 22-26% (2 g/day Niaspan); 17% (niacin immediate release 1.5 g/day); 20-22% (Niaspan 1.5 g/day)

Triglyceride decrease: 20-50%

Further LDL decrease: 1-5% (Niaspan 1 g/day); 10% (Niaspan 2 g/day)

Further HDL increase: 24% (Niaspan 2 g/day); 15-17% (Niaspan 1 g/day)

Further triglyceride decrease: 24% (Niaspan 2 g/day); 12-22% (Niaspan 1 g/day)

Secondary MI prevention; in combination with a resin, slows progression or promotes regression of atherosclerosis; reduces mortality

As statin add-on, reduces carotid intima-media thickness (surrogate marker) compared with ezetimibe as statin add-on in patients with lower HDL

No CV event benefit from niacin plus statin versus statin alone in patients with well-controlled LDL, low HDL, and high triglycerides

Option for triglyceride >500 mg/dL (about 5 mmol/L)

Raises HDL more than any other agent

Dose-dependent risk of hyperglycemia (especially in patients with type 2 diabetes) and liver toxicity

May increase risk of statin myopathy

Omega-3 ethyl esters LDL increase: 44.5% (4 g/day)

HDL increase: 9.1% (4 g/day)

Triglyceride decrease: 45% (4 g/day)

LDL increase: 0.7% (4 g/day)

Further HDL increase: 3.4% (4 g/day)

Further triglyceride decrease: 29.5% (4 g/day)

Secondary prevention: Reduces cardiovascular death; sudden death; and combined endpoint of death, nonfatal MI, and nonfatal stroke

Secondary prevention in patients with, or at risk for, type 2 diabetes: did not reduce CV events

Option for triglyceride >500 mg/dL (about 5 mmol/L)

Safe for use with statins

Associated with an increase in risk for recurrence of symptomatic atrial fibrillation or flutter within first 3 months of therapy

Use with caution with fish or shellfish allergy

Table 5. Statin Drug Characteristics [73]
Drug Potency (average LDL decrease) Renal Considerations Liver Function Monitoring
Atorvastatin 10 mg: 35-39%

20 mg: 43%

40 mg: 50%

80 mg: 55-60%

No dose adjustment necessary for reduced renal function Check liver function tests at baseline and when clinically indicated
Fluvastatin 20 mg: 22%

40 mg: 25%

80 mg: 35%

(as XL product)

In severe renal impairment, use daily doses >40 mg with caution Check liver function tests at baseline and when clinically indicated
Lovastatin 10 mg: 21%

20 mg: 24-27%

40 mg: 30-31%

80 mg: 40-42%

(as 40 mg BID)

If CrCl < 30 mL/min, use daily doses over 20 mg with caution Check liver function tests at baseline and when clinically indicated
Pitavastatin 1 mg: 31-32%

2 mg: 36-39%

4 mg: 41-45%

For glomerular filtration rate 15-59 mL/min/1.73 m2, including hemodialysis, initial daily dose is 1 mg, not to exceed 2 mg/day Check liver function tests at baseline and when clinically indicated
Pravastatin 10 mg: 22%

20 mg: 32%

40 mg: 34%

80 mg: 37%

In significant renal impairment, start with 10 mg/day Check liver function tests at baseline and when clinically indicated
Rosuvastatin 5 mg: 45%

10 mg: 46-52%

20 mg: 47-55%

40 mg: 55-63%

If CrCl < 30 mL/min/1.73 m2 (but not on hemodialysis), starting dose is 5 mg/day, not exceed 10 mg/day

Rosuvastatin levels in hemodialysis patients are about 50% higher than levels in normal renal function

Check liver function tests at baseline and when clinically indicated
Simvastatin 5 mg: 26%

10 mg: 30%

20 mg: 38%

40 mg: 29-41%

80 mg: 36-47%

In severe renal impairment, starting dose is 5 mg daily with close monitoring Check liver function tests at baseline and when clinically indicated
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.