What are the causes of isolated hypertriglyceridemia (elevated triglycerides)?

From the Guidelines

Isolated elevated triglycerides are primarily caused by lifestyle choices, genetic factors, and certain medical conditions, and the most effective approach to management is through lifestyle modifications, including weight loss, dietary changes, and increased physical activity, as recommended by the 2021 ACC expert consensus decision pathway 1.

Causes of Isolated Elevated Triglycerides

The causes of isolated elevated triglycerides can be multifactorial, including:

• Lifestyle factors such as excessive alcohol consumption, a diet high in refined carbohydrates and sugars, obesity, and physical inactivity
• Genetic causes, including familial hypertriglyceridemia and familial combined hyperlipidemia
• Medical conditions, such as uncontrolled diabetes, hypothyroidism, kidney disease, and liver disorders, including nonalcoholic fatty liver disease
• Certain medications, including some beta-blockers, diuretics, estrogens, retinoids, glucocorticoids, HIV antiretrovirals, and immunosuppressants like cyclosporine

Management of Isolated Elevated Triglycerides

The initial approach to managing isolated elevated triglycerides should focus on lifestyle modifications, including weight loss, dietary changes, and increased physical activity, as these interventions can lead to significant reductions in triglyceride levels, as noted in the 2021 ACC expert consensus decision pathway 1. Additional management strategies may include:

• Medications, such as fibrates, omega-3 fatty acids, statins, or niacin, which may be necessary if triglycerides remain significantly elevated despite lifestyle changes
• Evaluation and treatment of secondary causes of hypertriglyceridemia, such as diabetes, hypothyroidism, or kidney disease
• Consideration of the patient's overall cardiovascular risk profile and the potential benefits of reducing triglyceride levels on cardiovascular disease risk, as discussed in the 2019 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1.

From the FDA Drug Label

Excess body weight and excess alcoholic intake may be important factors in hypertriglyceridemia and should be addressed prior to any drug therapy. Diseases contributory to hyperlipidemia, such as hypothyroidism or diabetes mellitus should be looked for and adequately treated. Estrogen therapy, thiazide diuretics and beta-blockers, are sometimes associated with massive rises in plasma triglycerides, especially in subjects with familial hypertriglyceridemia Excess body weight and excess alcohol intake may be important factors in hypertriglyceridemia and should be managed prior to any drug therapy Diseases contributory to hyperlipidemia such as hypothyroidism or diabetes mellitus should be looked for and adequately treated. Estrogen therapy is sometimes associated with massive rises in plasma triglycerides, especially in subjects with familial hypertriglyceridemia

The causes of isolated elevated triglycerides include:

• Excess body weight
• Excess alcohol intake
• Diseases contributory to hyperlipidemia, such as:
  • Hypothyroidism
  • Diabetes mellitus
• Certain medications, such as:
  • Estrogen therapy
  • Thiazide diuretics
  • Beta-blockers 2 3

From the Research

Causes of Isolated Elevated Triglycerides

• Hypertriglyceridemia is associated with overweight, metabolic syndrome, and diabetes mellitus 4
• Common secondary causes of hypertriglyceridemia include obesity, uncontrolled diabetes, alcohol misuse, and various commonly used drugs 5
• Genetic factors can also play a role, with some patients having purely genetic types of hypertriglyceridemia, such as familial chylomicronemia syndrome 4, 5
• Lifestyle factors, such as diet and physical activity level, can also contribute to elevated triglyceride levels 4, 5

Risk Factors

• Elevated triglyceride levels are causally linked to cardiovascular disease and pancreatitis 4, 6, 7, 8
• Triglyceride levels above 1000 mg/dL (11.4 mmol/L) can induce acute pancreatitis 4
• Patients with severe hypertriglyceridemia have an increased incidence of pancreatitis and cardiovascular disease 6, 7, 8

Management

• Lifestyle modifications, such as cessation of alcohol consumption, reduced intake of rapidly metabolized carbohydrates, weight loss, and blood sugar control, are the most effective ways to lower triglyceride levels 4, 5
• Drug treatment, such as fibrates, omega-3 fatty acids, and niacin, may be necessary in some cases to lower triglyceride levels 4, 5, 6, 7
• Statins may also be used to reduce cardiovascular risk, but their efficacy in combination with other drugs has not been clearly shown in endpoint studies 4, 7