Background
While management of hyperlipidemia usually focuses on total and LDL cholesterol levels, very high triglyceride levels pose a risk for pancreatitis, and moderately high levels may confer cardiovascular risk. The Endocrine Society recently published a guideline to provide recommendations regarding the diagnosis, evaluation, and treatment of patients with hypertriglyceridemia.
Conclusions
In the National Health and Nutrition Examination Survey (NHANES) 1999-2004, 33% of participants had triglycerides of at least 150 mg/dL. The Endocrine Society has suggested classifying hypertriglyceridemia as follows, based on measurement of levels after a 12-hour fast: normal at less than 150 mg/dL, mild at 150-199 mg/dL, moderate at 200-999 mg/dL, severe at 1,000-1,999 mg/dL, and very severe at greater than 2,000 mg/dL.
Dr. Alice Alexander
The severe and very severe categories were included because they indicate risk for developing pancreatitis. There is less evidence to support categorizing levels from 150 mg/dL to 1,000 mg/dL, as the exact level at which serum triglycerides may confer risk for cardiovascular disease is unknown.
Several factors may contribute to elevated triglycerides. Lifestyle factors include overweight status, physical inactivity, a diet high in simple carbohydrates, and excess alcohol intake. Patients with untreated diabetes mellitus often have hypertriglyceridemia. Other endocrine disorders that can contribute to hypertriglyceridemia include acromegaly, hypothyroidism, and hypercortisolism. Renal disease and hepatic disease are associated with hypertriglyceridemia.
Certain medications, including estrogens, bile acid sequestrants, and protease inhibitors, can raise triglyceride levels. Certain second-generation antipsychotics, including clozapine, risperidone, quetiapine, and olanzapine, can cause secondary hyperlipidemia. Genetic disorders, including familial combined hyperlipidemia and familial hypertriglyceridemia, also cause hypertriglyceridemia.
There is a paucity of evidence regarding any causal relationship between serum triglycerides and atherosclerosis. The Women’s Health Study did not find an independent association between cardiovascular events and fasting triglycerides in 20,118 women. Meta-analyses of prospective cohort studies support a modest independent effect of serum triglycerides on the risk of cardiovascular disease, but there are no clear studies showing that reducing triglyceride levels reduces risk of cardiovascular disease.
Very severe triglyceride elevations (greater than 2,000 mg/dL) increase the risk of pancreatitis in the chylomicronemia syndrome. The specific mechanism by which chylomicronemia causes pancreatitis is unclear.
Implementation
Screen adults for hypertriglyceridemia with a fasting lipid panel at least every 5 years. The length of fast is recommended to be at least 12 hours.
• Assessment of lipoprotein particle size and heterogeneity is not recommended, as there is a lack of evidence to support using lipoprotein heterogeneity as a therapeutic target.
• Evaluate patients with hypertriglyceridemia for secondary causes, including endocrine disorders (the most common of which is inadequately treated diabetes mellitus).
• Evaluate patients with primary hypertriglyceridemia for other cardiovascular risk factors.
• Lifestyle therapy is recommended as the initial treatment for mild to moderate hypertriglyceridemia. Reduced intake of sugar-sweetened beverages and of high glycemic index foods will lower serum triglycerides. Exercise and weight loss are also important components of triglyceride reduction.
• The three drug classes that reduce triglycerides (fibrates, niacin, and n-3 fatty acids) alone or in combination with statins may be considered as treatment options in patients with moderate to severe hypertriglyceridemia. This is a weak recommendation, as the evidence to support treating moderate hypertriglyceridemia is low quality.
• Treatment of moderate hypertriglyceridemia with fibrates has not been shown to reduce cardiovascular or total mortality. Niacin has had a proven benefit in decreasing cardiovascular events, but it has significant adverse effects, including hepatotoxicity, hyperuricemia, and hyperglycemia. Niacin has not been shown to have any additive benefit in reducing cardiovascular events in patients who are already taking a statin and who have mild hypertriglyceridemia. No studies have shown that treatment of hypertriglyceridemia with omega-3 fatty acids reduces cardiovascular events.
• Statins have a modest triglyceride-lowering effect. They should not be used as monotherapy for severe or very severe hypertriglyceridemia, but they may be indicated in the treatment of patients who have moderate hypertriglyceridemia and risk factors for cardiovascular disease.
• For severe and very severe hypertriglyceridemia, drug therapy plus lifestyle change is recommended to reduce the risk of pancreatitis. Patients with very severe hypertriglyceridemia should reduce dietary intake of saturated and unsaturated fat. This recommendation is supported by high-quality evidence.
• Fibrates are first-line treatment in patients with severe or very severe hypertriglyceridemia. LDL cholesterol levels may increase during treatment in patients with very severe hypertriglyceridemia. A treatment goal of less than 1,000 mg/dL is recommended. Fibrates are contraindicated in patients with liver and gallbladder disease and should be used with caution in renal disease. Fenofibrate is the preferred fibrate to use in combination with a statin.