Guidelines issued for evaluation, treatment of hypertriglyceridemia

Eliot A. Brinton, MD, FAHA, FNLA

The new Endocrine Society Clinical Practice Guideline on Hypertriglyceridemia is in some ways similar and in some ways quite different from three other major current clinical triglyceride guidelines:

1. The Third National Cholesterol Education Program Adult Treatment Panel (NCEP/ATP-III—2002),
2. The European Atherosclerosis Society Consensus Panel on TG-rich lipoproteins and HDL in patients at high risk for CVD (2011), and
3. The American Heart Association Scientific Statement on Triglycerides and CVD (2011) For example, “normal” (or “desirable”) triglyceride levels are defined by all four guidelines as less than 150 mg/dL. Also, triglyceride levels of 150 mg/dL to 200 mg/dL are defined in the Endocrine Society Guideline as “mild hypertriglyceridemia,” which sound similar to “borderline triglycerides” for the same range in NCEP/ATP-III and the AHA statement.

There are significant differences, however, between the Endocrine Society Guideline and the others in categorization of triglyceride levels above 200 mg/dL. The Endocrine Society Guideline provides three categories for triglyceride levels over 200 mg/dL:

1. 200 mg/dL to 999 mg/dL is “Moderate” hypertriglyceridemia;
2. 1,000 mg/dL to 1,999 mg/dL is “Severe” hypertriglyceridemia; and
3. 2,000 mg/dL and greater is “Very Severe” hypertriglyceridemia.

In contrast, NCEP/ATP-III and the AHA statement both have only two, much lower, categories in this range (triglycerides ranging from 200 mg/dL to 499 mg/dL being “high” triglycerides, and 500 mg/dL and greater being “very high.” These distinctions in triglyceride categories are important in clinical treatment recommendations because both NCEP/ATP-III and AHA suggest primary focus on triglyceride-lowering for risk of pancreatitis at triglycerides of 500 mg/dL or greater, whereas the Endocrine Society guidelines suggest that such treatment start at double that level — 1,000 mg/dL or greater.

Similar to the other guidelines, the Endocrine Society Guideline provides a detailed analysis of the increase in CVD risk in most patients with hypertriglyceridemia, although it admits that it is still not known if hypertriglyceridemia is directly causal of CVD or simply a marker of other causal factors The Endocrine Society Guideline also provides a lengthy, and clinically useful, list of secondary causes of triglyceride elevation, as does the AHA statement.

The Endocrine Society Guideline is similar to the NCEP/ATP-III and AHA Statement in advocating use of a fasting sample for triglyceride measurement, and all of these differ from the EAS Consensus Panel which highlights the potential utility of non-fasting triglyceride levels (which frankly is more of a tool for research than for clinical practice).

The Endocrine Society Guideline, however, is the first triglyceride guideline to state explicitly that:

1. Apo B measurements can be useful in the workup of patients with high triglycerides;
2. Measurements of LDL and HDL size are not useful in this context; and
3. Testing for elevated Lp(a) levels is useful in patients with hypertriglyceridemia. (This last point is rather curious because Lp(a) levels are not known to have any connection to hypertriglyceridemia.)

Diet and lifestyle treatment recommendations are generally similar among the various guidelines (which all advocate lower sugar and fat intake, weight loss for obesity and physical activity) although the Endocrine Society Guideline appears to be the first to suggest that increased protein intake might help lower triglyceride levels.

Finally, although all four guidelines highlight the same four classes of medications (fibrates, omega-3, niacin and statins) the Endocrine Society Guideline is the first to explicitly recommend against statin monotherapy for triglcyeride levels over 1,000 mg/dL, and the first explicitly to recommend fibrates (only) as first-line therapy for prevention of pancreatitis in patients with severe and very severe hypertriglyceridemia.

In summary, the new Endocrine Society Guideline for Evaluation and Treatment of Hypertriglyceridemia serves as another reminder that patients with hypertriglyceridemia are at high risk for CVD and possibly pancreatitis, and so they require evaluation for the severity, secondary causes and treatment of their elevated triglyceride levels. This guideline then clarifies recommended ways to perform these tasks.

Despite the importance of hypertriglyceridemia in the risk for pancreatitis and CVD, high triglyceride levels are all too often neglected by busy cardiologists in their routine clinical practice. Attention to the fasting standard lipid panel, possibly with an ApoB measurement, assessment and control of any secondary factors (including lifestyle, diseases and medications), and direct medical treatment, as needed, all appear to be essential to adequate management of elevated triglyceride levels, which may be seen in up to 10% of patients at high risk for CVD or with a history of prior events.