Hypertriglyceridemia: Treatment

Authors and Disclosures

Treatment

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 [SOR-B].^[1,4,5] The relationship between triglycerides and cardiovascular disease is less clear. There have been multiple conflicting studies regarding the role of triglycerides and the development of CHD.^[8-12] Hypertriglyceridemia is clearly associated with CHD in univariate analysis. However, many multivariate studies have shown that its risk is markedly attenuated after adjustment for other strong CHD risk factors, namely, low HDL levels and increased small, dense LDL particles. These findings have led some researchers to believe that hypertriglyceridemia serves more as a proxy for abnormal cholesterol levels and cholesterol sub-fractions of which hypertriglyceridemia is frequently associated.^[13] Most interventions aimed at lowering the triglyceride level also raise the HDL level, which is well known for reducing coronary events [SOR-B].^[9,10] A recent review of the literature concluded that treating isolated hypertriglyceridemia does not prevent coronary events.^[14] However, a thorough search for other components of the metabolic syndrome is recommended.

On the other hand, there have been many other studies that have shown hypertriglyceridemia to be an independent risk factor for CHD even after adjustment for HDL and LDL.^[9,15-17] Furthermore, the NCEP considers hypertriglyceridemia to be an independent risk factor for CHD and calls for medical treatment in cases where therapeutic lifestyle changes (TLC) are not adequate to reduce the triglycerides to appropriate levels.^[1] Although the extent to which hypertriglyceridemia causes CHD is controversial at present, the authors feel that because most cases of hypertriglyceridemia are associated with abnormal cholesterol sub-fractions and are frequently found in patients with CHD risk factors, treatment of hypertriglyceridemia is often warranted in conjunction with the necessary treatment of the other lipid derangements. In cases where hypertriglyceridemia is found to be the only lipid abnormality, treatment is still important to prevent pancreatitis when triglycerides are markedly elevated.

The treatment of hypertriglyceridemia begins with TLC. Specifically, a low fat, carbohydrate-controlled diet should be adopted. Saturated fat should not make up more than 7% of total daily calories, carbohydrates should be restricted to 50% to 60% of daily calories, and simple sugars like sucrose should be avoided.^[1] Patients may also consider increasing intake of oily fish (eg, salmon, mackerel, herring) to at least 2 servings per week.^[18] Alcohol should be greatly reduced or stopped altogether, along with smoking cessation if indicated. Discontinuation of any offending medications should be considered as well. Titration upwards to a goal of at least 30 minutes of aerobic exercise 5 days a week is greatly beneficial. If present, diabetes and hypothyroidism should be treated accordingly. These measures often have a dramatic effect on triglyceride levels and can lower it hundreds of points.^[1]

If TLC and control of secondary medical conditions are not adequate to lower the triglyceride level to <200 mg/dL, then medical therapy is warranted (Figure 1). When triglyceride levels range between 200 mg/dL and 500 mg/dL, treatment should be directed primarily toward normalizing the LDL cholesterol.^[1] Once the LDL is at goal, a secondary endpoint is the non-HDL cholesterol (total cholesterol-HDL). Non-HDL goals are 30 mg/dL higher than LDL goals. A tertiary treatment goal, particularly in the setting of CHD or CHD risk equivalents, is to raise the HDL to >40 mg/dL. The benefit of medically treating triglyceride levels between 200 mg/dL and 500 mg/dL when the other lipid sub-fractions are normal is less clear and medical management in these patients should be individualized ( Table 7 ).^[14]

(Enlarge Image)

Figure 1. Treatment Algorithm.

In cases of isolated hypertriglyceridemia, fibrates, such as gemfibrozil and fenofibrate, may be used because they are potent reducers of triglycerides. Furthermore, fish oil supplementation may be added to augment the fibrate treatment, and in some cases, the patient may elect to try fish oil supplementation as first line. Fish oils have a dose-dependent effect and many patients will need 2 g to 4 g a day of fish oil supplementation to achieve goals. Omega-3 fatty acids (4 g per day) will reduce triglyceride levels by 30%.^[19,20] However, at this dosage, omega-3 will elevate the LDL by 5% to 10% and will have little effect on the HDL.^[20] Fish oil capsules can be taken at any time of the day, with or without food, together or in divided doses. However, as the capsules dissolve in the stomach and release the oil, many people experience a "fishy burp." Taking the capsule at bedtime, freezing them, taking enteric-coated capsules, or taking them with food may minimize or eliminate this problem.^[21]

In many circumstances, the LDL is elevated in addition to the triglycerides. In these cases, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) should be used to lower the LDL to the patient's goal based on NCEP ATP III guidelines.^[1] Niacin or fibrates may be added if the LDL and/or the triglycerides remain too high. 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. This combination particularly should be avoided in the elderly, in patients with acute or serious chronic illnesses (especially chronic renal disease), in those undergoing surgery, and in patients receiving multiple medications.^[22]

For other mixed dyslipidemias involving high triglycerides and low HDL, niacin may be considered. There are 3 available preparations of niacin: immediate acting, long acting, and extended release. Immediate acting niacin must be taken 3 times daily and is associated with flushing, hyperglycemia, and gastrointestinal side effects. The long-acting preparation can be taken once daily and has less flushing. However, with its absorption time lasting generally greater than 12 hours, it carries a higher risk of hepatotoxicity and therefore is not recommended. The best preparation of niacin to be prescribed is extended release (ER) niacin.^[23] ER niacin has a lower rate of flushing and no additional risk of hepatotoxicity as is found with the long-acting preparations. Furthermore, ER niacin can be dosed once daily resulting in better adherence because it is typically absorbed over 8 to 12 hours. ER niacin has been shown to lower the triglyceride level by ~25% and raise the HDL level by almost 30%.^[24] To prevent flushing, a low starting dose of niacin should be taken immediately after the evening meal and increased at monthly intervals. In addition, aspirin (325 mg) may be taken 30 to 60 minutes before any form of niacin to further reduce the incidence of flushing. Niacin should be used with caution in patients with diabetes (including glucose intolerance) and gout as it may increase blood sugar and uric acid levels, respectively. Niacin is contraindicated in patients with active peptic ulcer disease.

Finally, it is important to note that patients with severe hypertriglyceridemia (over 1000 mg/dL) often need a combination of medicines to achieve their goal (Figure 1). In addition, they will benefit from strict adherence to TLC including a very low fat diet and complete abstinence from alcohol. If patients do not reach their goals with the above treatment regimens, a referral to a lipid specialist and medical dietician may be warranted. In addition, keep in mind that some physicians may be tempted to add bile acid binding resins to help treat elevated total cholesterol and LDL. However, these medications can worsen triglyceride levels and should not typically be used in patients with significantly elevated triglycerides.^[25,26]

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J Am Board Fam Med. 2006;19(3):310-316. © 2006 American Board of Family Medicine

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• Hypertriglyceridemia Is Common Among US Adults

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• Both Fish Oil and Fibrates Reduce Triglyceride Levels
• The Role of Omega-3 Fatty Acids in Cardiovascular Disease, Hypertriglyceridaemia and Diabetes Mellitus