Diagnosis and Definitions
- Severe and very severe hypertriglyceridemia increase the risk for pancreatitis, whereas mild or moderate hypertriglyceridemia may be a risk factor for cardiovascular disease. Therefore, similar to the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III guideline committee’s recommendations, the Endocrine Society recommends screening adults for hypertriglyceridemia as part of a lipid panel at least every 5 yr (1|⊕⊕oo).
- Base the diagnosis of hypertriglyceridemia on fasting triglyceride levels and not on nonfasting triglyceride levels (1|⊕⊕⊕o).
- AVOID the routine measurement of lipoprotein particle heterogeneity in patients with hypertriglyceridemia (1|⊕⊕oo). Measurement of apolipoprotein B (apoB) or lipoprotein(a) [Lp(a)] levels can be of value, whereas measurement of other apolipoprotein levels has little clinical value (2|⊕⊕oo).
Causes of elevated triglycerides—primary and secondary
- Evaluate individuals found to have any elevation of fasting triglycerides for secondary causes of hyperlipidemia including endocrine conditions and medications. Focus treatment on such secondary causes (1|⊕⊕oo).
- Assess patients with primary hypertriglyceridemia for other cardiovascular risk factors such as central obesity, hypertension, abnormalities of glucose metabolism, and liver dysfunction (1|⊕⊕oo).
- Evaluate patients with primary hypertriglyceridemia for family history of dyslipidemia and cardiovascular disease to assess genetic causes and future cardiovascular risk (1|⊕⊕oo).
Table 1. Causes of Hypertriglyceridemia
- Familial combined hyperlipidemia
- Familial hypoalphalipoproteinemia
- Familial hypertriglyceridemia
- Familial chylomicronemia and related disorders
- Familial dysbetalipoproteinemia
Primary genetic susceptibility
- Metabolic syndrome
- Treated type 2 diabetes
- Excess alcohol intake
- Renal disease
- Drug-induced (eg, thiazides,
β-blockers, estrogens, isotretinoin,
corticosteroids, bile acid-binding
resins, antiretroviral protease
- Liver disease
- Untreated diabetes mellitus
- Endocrine diseases
- Autoimmune disorders
Table 2. Criteria Proposed for Clinical Diagnosis of Elevated Triglyceride Levels Under Fasting Conditions
|NCEP ATP III (3)||The Endocrine Society 2010a|
|1.7-2.3 mmol/liter||Mild HTG||150-199|
|2.3-5.6 mmol/liter||Moderate HTG||200-999|
|Very high triglycerides||≥500|
|≥5.6 mmol/liter||Severe HTG||1000-1999 mg/dL||11.2-22.4 mmol/liter|
|Very severe HTG||≥2000|
a The criteria developed for the present guidelines focus on the ability to assess risk for premature CVD vs. risk for pancreatitis. The designations of mild and moderate hypertriglyceridemia correspond to the range of levels predominant in risk assessment for premature CVD, and this range includes the vast majority of subjects with hypertriglyceridemia. Severe hypertriglyceridemia carries a susceptibility for intermittent increases in levels above 2000 mg/dL and subsequent risk of pancreatitis; very severe hypertriglyceridemia is indicative of risk for pancreatitis. In addition, these levels suggest different etiologies. Presence of mild or moderate hypertriglyceridemia is commonly due to a dominant underlying cause in each patient, whereas severe or very severe hypertriglyceridemia is more likely due to several contributing factors.
Management of Hypertriglyceridemia
- The initial treatment of mild-to-moderate hypertriglyceridemia should be lifestyle therapy, including dietary counseling to achieve appropriate diet composition, physical activity, and a program to achieve weight reduction in overweight and obese individuals (1|⊕⊕oo).
- For severe and very severe hypertriglyceridemia (>1000 mg/dL), combine reduction of dietary fat and simple carbohydrate intake with drug treatment to reduce the risk of pancreatitis (1|⊕⊕⊕⊕).
- The treatment goal for patients with moderate hypertriglyceridemia is a non-high-density lipoprotein (HDL) cholesterol level in agreement with NCEP ATP guidelines (1|⊕⊕oo).
- Use a fibrate as a first-line agent for reduction of triglycerides in patients at risk for triglyceride-induced pancreatitis (1|⊕⊕⊕o).
- Consider three drug classes (fibrates, niacin, n-3 fatty acids) alone or in combination with statins as treatment options in patients with moderate to severe triglyceride levels (2|⊕⊕oo).
- DO NOT use statins as monotherapy for severe or very severe hypertriglyceridemia. However, statins may be useful for the treatment of moderate hypertriglyceridemia when indicated to modify cardiovascular risk (1|⊕⊕oo).
- Fibrates should be strongly considered in patients with severe and very severe hypertriglyceridemia and should be considered in patients with moderate hypertriglyceridemia. Fibrates decrease triglyceride levels by 30–50% and sometimes increase HDL cholesterol
- Fibric acid derivatives should be used with great caution in the setting of renal insufficiency because the drugs are excreted in the urine and may reversibly increase serum creatinine levels— especially fenofibrate, although the significance of this effect is unknown. Fenofibrate, which does not interfere with statin metabolism and has a lower risk of causing myopathy, is the preferred fibrate to use in combination with a statin. Due to effects on protein binding, there is a potential interaction with warfarin requiring careful monitoring.
- Gemfibrozil can be considered in very severe hypertriglyceridemia beginning in the second trimester in pregnant women who are at risk of pancreatitis.
- Clinical trials using niacin, alone or in combination with other lipid medications, have shown benefits in decreasing cardiovascular event rates and atherosclerosis.
- The most common side effect is cutaneous flushing, which is most significant with the first few doses. The most serious complication of niacin therapy is dose dependent hepatotoxicity, and therapy should be accompanied by monitoring of liver function tests. Other side effects of niacin therapy include impairment or worsening of glucose tolerance and hyperuricemia.
- Niacin is contraindicated in patients with active peptic ulcer disease.
n-3 Fatty acids
- The long-chain marine omega-3 fatty acids [eicosapentaenoic acid, C20:5n-3 (EPA) and docosahexaenoic acid, C22:6n-3 (DHA)] lower fasting and postprandial triglyceride levels in a dose-dependent fashion.
- Side effects with large doses of omega-3 fatty acids include fishy taste and burping.