Am Fam Physician. 2020;102(6):347-354
Related letter: Clinical Considerations for the Management of Hypertriglyceridemia
Author disclosure: No relevant financial affiliations.
Hypertriglyceridemia, defined as fasting serum triglyceride levels of 150 mg per dL or higher, is associated with increased risk of cardiovascular disease. Severely elevated triglyceride levels (500 mg per dL or higher) increase the risk of pancreatitis. Common risk factors for hypertriglyceridemia include obesity, metabolic syndrome, and type 2 diabetes mellitus. Less common risk factors include excessive alcohol use, physical inactivity, being overweight, use of certain medications, and genetic disorders. Management of high triglyceride levels (150 to 499 mg per dL) starts with dietary changes and physical activity to lower cardiovascular risk. Lowering carbohydrate intake (especially refined carbohydrates) and increasing fat (especially omega-3 fatty acids) and protein intake can lower triglyceride levels. Moderate- to high-intensity physical activity can lower triglyceride levels, as well as improve body composition and exercise capacity. Calculating a patient's 10-year risk of atherosclerotic cardiovascular disease is pertinent to determine the role of medications. Statins can be considered for patients with high triglyceride levels who have borderline (5% to 7.4%) or intermediate (7.5% to 19.9%) risk. For patients at high risk who continue to have high triglyceride levels despite statin use, high-dose icosapent (purified eicosapentaenoic acid) can reduce cardiovascular mortality (number needed to treat = 111 to prevent one cardiovascular death over five years). Fibrates, omega-3 fatty acids, or niacin should be considered for patients with severely elevated triglyceride levels to reduce the risk of pancreatitis, although this has not been studied in clinical trials. For patients with acute pancreatitis associated with hypertriglyceridemia, insulin infusion and plasmapheresis should be considered if triglyceride levels remain at 1,000 mg per dL or higher despite conservative management of acute pancreatitis.
Hypertriglyceridemia is defined as fasting serum triglyceride levels of 150 mg per dL (1.69 mmol per L) or higher. Elevated triglyceride levels (150 to 499 mg per dL [1.69 to 5.64 mmol per L]) are associated with increased risk of cardiovascular disease (CVD), and severely elevated levels (500 mg per dL [5.65 mmol per L] or higher) are associated with increased risk of pancreatitis. (Table 1).1 This article answers commonly asked questions related to the management of hypertriglyceridemia.
WHAT'S NEW ON THIS TOPIC
Systematic reviews consistently do not support use of omega-3 fatty acids for the primary prevention of cardiovascular disease.
For patients with established cardiovascular disease and elevated triglyceride levels who are already on statins, icosapent (Vascepa) reduces cardiovascular mortality (number needed to treat = 111 to prevent one cardiovascular death over five years) but may not be cost-effective. Currently, treatment of 111 patients to prevent one cardiovascular death would cost approximately $1.8 million.
| Clinical recommendation | Evidence rating | Comments |
|---|---|---|
| Encourage weight loss of 5% or more to lower triglyceride levels and improve risk factors for CVD.2,3 | C | Weight loss and reduction of visceral adiposity through nutrition and an exercise program; consensus and disease-oriented evidence |
| Advise a lower-carbohydrate and higher-fat or higher-protein diet for those with triglyceride levels lower than 500 mg per dL (5.65 mmol per L).2,3,19,20 | C | Simple carbohydrates, including fructose, can increase fatty acid production in the liver; consensus and disease-oriented evidence |
| Prescribe fibrates and omega-3 fatty acids for patients with triglyceride levels of 500 mg per dL or higher to reduce the risk of pancreatitis.1–4 | C | Risk increases with triglyceride levels of 1,000 mg per dL (11.30 mmol per L) or higher; consensus, standard practice, and expert opinion |
| Consider statins in patients with triglyceride levels between 150 and 499 mg per dL (1.69 to 5.64 mmol per L) and borderline or intermediate cardiovascular risk.1,2,10 | C | Hypertriglyceridemia is a risk-enhancing factor for CVD; consensus and expert opinion |
| Consider icosapent (Vascepa) for patients with elevated triglyceride levels (150 to 499 mg per dL) and established CVD who are taking statins.4,39 | B | Patients randomized to icosapent, 4 g daily, had lower cardiovascular mortality (number needed to treat = 111 to prevent one cardiovascular death over five years); one large randomized controlled trial |
| Classification | Triglyceride level |
|---|---|
| Normal | Less than 150 mg per dL (1.69 mmol per L) |
| High | 150 to 499 mg per dL (1.69 to 5.64 mmol per L) |
| Severe | 500 mg per dL (5.65 mmol per L) or greater |
What Are the Risk Factors for Hypertriglyceridemia?
Common risk factors are obesity, metabolic syndrome, and type 2 diabetes mellitus. Less common risk factors include excessive alcohol use (more than two standard drinks daily in men and more than one standard drink daily in women), physical inactivity, being overweight, use of certain medications (e.g., atypical antipsychotics, antiretroviral protease inhibitors, beta blockers, bile acid–binding resins, corticosteroids, estrogens, immunosuppressants, isotretinoin, thiazide diuretics), and genetic disorders.2,3 Risk factors for hypertriglyceridemia are summarized inTable 2. 1,2,4
| Risk factors | Causes |
|---|---|
| Common risk factors | |
| Metabolic syndrome (increased waist circumference; reduced high-density lipoprotein cholesterol levels; and elevated triglyceride levels, glucose levels, and blood pressure) | Insulin resistance, visceral adiposity, and increased fatty acid production |
| Type 2 diabetes mellitus | Insulin resistance and decreased activity of lipoprotein lipase |
| Secondary hypertriglyceridemia | |
| Excess alcohol intake* | Increased liver production of fatty acids |
| Medication use | Atypical antipsychotics, antiretroviral protease inhibitors, beta blockers, bile acid–binding resins, corticosteroids, estrogens, immunosuppressants, isotretinoin, thiazide diuretics |
| Endocrine disease | Hypothyroidism-related dyslipidemia |
| Renal disease | Decreased clearance of triglyceride-rich lipoproteins |
| Liver disease | Nonalcoholic fatty liver disease |
| Pregnancy | Estrogen mediated |
| Autoimmune disorders | Antibodies directed against lipoprotein lipase |
| Primary hypertriglyceridemia | |
| Genetic disorders | Familial combined hyperlipidemia, familial hypertriglyceridemia, familial dysbetalipoproteinemia, familial hypoalphalipoproteinemia, familial hyperchylomicronemia, and related disorders |
EVIDENCE SUMMARY
Hypertriglyceridemia is associated with increasing age, higher body mass index, elevated blood glucose levels, elevated total cholesterol, and reduced high-density lipoprotein (HDL) cholesterol. Up to 33% of adults in the United States have triglyceride levels of 150 mg per dL or higher.5 In studies using a cutoff of 200 mg per dL (2.26 mmol per L), 17.9% of patients had elevated triglyceride levels, and 1.7% to 2.1% had severely elevated triglyceride levels.5,6 In one study, 0.4% of patients had triglyceride levels of 1,000 mg per dL (11.30 mmol per L) or higher.6
After hypertriglyceridemia is identified, the patient should be assessed for common and secondary causes. Common risk factors for hypertriglyceridemia include obesity, metabolic syndrome, and type 2 diabetes.2,3 The National Health and Nutrition Examination Survey showed that 80% of the U.S. population have one or more criteria for metabolic syndrome.7 Other risk factors include excessive alcohol consumption (more than two standard drinks daily for men and more than one standard drink daily for women), physical inactivity, being overweight, medication use, endocrine disorders, and autoimmune disorders.1–3 Other genetic syndromes cause hypertriglyceridemia but are beyond the scope of this article.
What Is the Clinical Significance of Hypertriglyceridemia?
The American College of Cardiology/American Heart Association cholesterol guidelines list hypertriglyceridemia as a risk-enhancing factor for CVD.1,8 It is also a component of metabolic syndrome and is a feature of atherogenic dyslipidemia (hypertriglyceridemia and low HDL cholesterol levels). Despite the association between hypertriglyceridemia and CVD, studies have not demonstrated a reduction in cardiovascular events or deaths with the treatment of isolated hypertriglyceridemia. Hypertriglyceridemia is also a risk factor for acute pancreatitis.1,9
EVIDENCE SUMMARY
The American College of Cardiology/American Heart Association guidelines list elevated triglyceride levels as a risk-enhancing factor for CVD.1,8 Risk-enhancing factors may confer additional cardiovascular risk beyond traditional major risk factors (e.g., cigarette smoking, diabetes, hypertension, low-density lipoprotein [LDL] cholesterol levels). Hypertriglyceridemia is a component of metabolic syndrome, which is also associated with an increased risk of CVD.10 Patients with hypertriglyceridemia and an increased waist circumference (40 inches for White males and 35 inches for White females) appear to be at higher risk of CVD.3
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