Update on the Endocrine Society Practice Guidelines for Evaluation and Treatment of Hypertriglyceridemia

Clinical practice guidelines have been established for the evaluation and treatment of hypertriglyceridemia (HTG) by an expert task force. Select members of the panel discussed goals of the guidelines, pertinent evidence, and remaining areas of uncertainty at ENDO 2013: The Endocrine Society’s 95^th Annual Meeting and Expo in San Francisco on June 17, 2013. These guidelines were published in the Journal of Clinical Endocrinology and Metabolism in September 2012.

Generally speaking, the task force wished to maintain a relationship with commonly used, well-established guidelines, such as those from the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III. However, previous guidelines for evaluation and treatment have focused on HDL cholesterol, rather than triglycerides (TGs). For this reason and due to recent evidence more firmly demonstrating an association between TGs and cardiovascular (CV) disease, the task force set forth to clarify evaluation and treatment recommendations as they apply to HTG.

According to Lars Berglund, MD, PhD, the panel chairman, HTG is a fairly common condition, affecting approximately 30% of the population. Genetic and secondary causes of HTG were reviewed, as were established HTG classifications. For the purpose of these new guidelines, the panel considered triglycerides (TGs) as a risk factor for cardiovascular disease versus as a risk factor for pancreatitis. In doing so, they expanded the NCEP ATP III classification for hypertriglyceridemia severity levels. Because TGs < 1000 mg/dL are perceived as relatively low risk for pancreatitis, the task force focused on TGs > 1000 mg/dL as a risk factor for pancreatitis.

Another goal of the task force was to clarify the use of fasting versus non-fasting TG levels. A number of recent studies, including MRFIT, the Copenhagen City Heart Study, and the Women’s Health Study have suggested an association between non-fasting TGs and CV disease in the general population. However, each of these studies has methodological flaws. According to the panel, there are still issues to be resolved regarding use of non-fasting TGs: standardization of collection procedures, the need to establish reference levels, and the impact of variability in the postprandial time period. The consensus recommendation is to base HTG diagnosis on fasting TG levels.

Consensus recommendations for evaluation and screening for HTG include obtaining a fasting TG level in adults every 5 years. If this level is elevated, the clinician is encouraged to assess for secondary causes of HTG. If HTG is found to be primary, the patient should be assessed for other risk factors. If secondary, the patient should be evaluated for family history of HTG and CV disease.

In regards to treatment recommendations, lifestyle modification, including dietary change and normalization of weight, is the recommendation for initial treatment for mild to moderate HTG. For those with severe and very severe HTG, focus should be on lifestyle modifications (especially decreasing intake of dietary fat and simple carbohydrates) in combination with medication.

John D. Brunzell, MD, presented the panel’s recommendations for medication therapy. Fibrates are effective at reducing TG levels and should be used for patients at risk for TG-induced pancreatitis. The panel also recommends consideration of fibrates for moderate, severe, and very severe HTG, citing a previously published a priori analysis that suggested a 10% reduction in CV events with fibrates but without any effect on overall mortality. It was additionally noted that there was a significant increase in death in women treated with fenofibrate, which should be considered.

The panel does not recommend statins as monotherapy for severe or very severe HTG. Other medications for consideration to be used alone or in combination therapy with statins include niacin and fish oil/omega-3 fatty acids. Brunzell reviewed a large meta-analysis published in 2012 that did not find any reduction in all-cause mortality or CV events with omega-3 fatty acids. Additionally, large studies such as AIM-HIGH evaluating the use of niacin did not show any benefit when added to a statin. Niacin use is also associated with adverse events and side effects. The panel recognizes the role of combination therapy as dictated by desired mechanism of action and encourages caution when initiating combination treatment.

All task force members disclosed Financial or Business/Organizational Interests but received no corporate funding or remuneration for participation in this task force.