What is the treatment for hypertriglyceridemia?

Treatment for Triglycerides of 215 mg/dL

Primary Recommendation

For a triglyceride level of 215 mg/dL (classified as moderate hypertriglyceridemia), initiate aggressive lifestyle modifications immediately, including 5-10% weight loss, restricting added sugars to <6% of total calories, limiting total fat to 30-35% of calories, and engaging in at least 150 minutes per week of moderate-intensity aerobic activity. 1 If you have a 10-year ASCVD risk ≥7.5% or elevated LDL-C, start moderate-intensity statin therapy (atorvastatin 10-20 mg or rosuvastatin 5-10 mg daily), which will reduce triglycerides by 10-30% while addressing cardiovascular risk. 1, 2

Classification and Risk Context

• A triglyceride level of 215 mg/dL falls into the moderate hypertriglyceridemia category (200-499 mg/dL), which is associated with increased cardiovascular risk but is below the threshold for acute pancreatitis concern (≥500 mg/dL). 1, 2
• This level constitutes a cardiovascular risk-enhancing factor when persistently elevated, warranting intervention to reduce long-term cardiovascular disease risk. 1
• The primary goal is to reduce triglycerides to <200 mg/dL (ideally <150 mg/dL) and achieve a non-HDL-C target of <130 mg/dL (calculated as total cholesterol minus HDL-C). 1

Immediate Assessment for Secondary Causes

Before initiating any pharmacologic therapy, you must evaluate for and address secondary causes, as these are often the primary drivers of hypertriglyceridemia: 1, 3

• Uncontrolled diabetes mellitus: Check HbA1c and fasting glucose; optimizing glycemic control can dramatically reduce triglycerides independent of lipid medications. 1
• Hypothyroidism: Check TSH, as thyroid dysfunction is a common reversible cause. 1
• Excessive alcohol intake: Even 1 ounce per day increases triglycerides by 5-10%; complete abstinence may be necessary. 1, 3
• Medications: Review for thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, and antipsychotics, which can significantly elevate triglycerides. 1
• Renal disease: Assess kidney function, as chronic kidney disease contributes to disordered triglyceride metabolism. 1

Lifestyle Modifications (First-Line Therapy)

Lifestyle changes are the cornerstone of treatment and can reduce triglycerides by 20-50%: 1, 4

Weight Loss and Physical Activity

• Target 5-10% body weight reduction, which produces a 20% decrease in triglycerides; in some patients, weight loss can reduce levels by up to 50-70%. 1, 5
• Engage in at least 150 minutes per week of moderate-intensity aerobic activity (or 75 minutes per week of vigorous activity), which reduces triglycerides by approximately 11%. 1, 2

Dietary Modifications

• Restrict added sugars to <6% of total daily calories and eliminate all sugar-sweetened beverages, as sugar intake directly increases hepatic triglyceride production. 1, 2
• Limit total fat to 30-35% of total daily calories for moderate hypertriglyceridemia. 1, 2
• Restrict saturated fats to <7% of total calories, replacing with polyunsaturated or monounsaturated fats. 1
• Consume at least 2 servings per week of fatty fish (salmon, trout, sardines) rich in omega-3 fatty acids. 1
• Increase soluble fiber to >10 g/day from whole grains, legumes, and vegetables. 1
• Limit or completely avoid alcohol consumption, as alcohol synergistically increases triglycerides. 1, 2

Pharmacologic Therapy Algorithm

If 10-Year ASCVD Risk ≥7.5% or Elevated LDL-C

Initiate moderate-intensity statin therapy (atorvastatin 10-20 mg or rosuvastatin 5-10 mg daily) as first-line pharmacologic treatment. 1, 2 Statins provide:

• 10-30% dose-dependent triglyceride reduction 1
• Proven cardiovascular risk reduction in randomized controlled trials 6
• Simultaneous LDL-C lowering, addressing the primary cardiovascular risk factor 6

If Triglycerides Remain >200 mg/dL After 3 Months

If triglycerides remain elevated after 3 months of optimized lifestyle modifications and statin therapy (if indicated), consider adding: 1

Prescription omega-3 fatty acids (icosapent ethyl 2-4 g daily) if you have: 1, 2

• Established cardiovascular disease, OR
• Diabetes with ≥2 additional risk factors
• This provides a 25% reduction in major adverse cardiovascular events (number needed to treat = 21) 1
• Monitor for increased risk of atrial fibrillation 1

Fenofibrate 54-160 mg daily if omega-3 criteria are not met: 1, 3

• Reduces triglycerides by 30-50% 1, 3
• Should be taken with meals to optimize bioavailability 3
• Requires monitoring for myopathy risk, especially if combined with statins 1

If 10-Year ASCVD Risk <7.5% and Normal LDL-C

Continue aggressive lifestyle modifications for 3 months, then reassess. 1 If triglycerides remain >200 mg/dL after optimal lifestyle changes:

• Consider fenofibrate 54-160 mg daily 1, 3
• Reassess fasting lipid panel in 4-8 weeks after initiating therapy 1

Monitoring Strategy

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications. 1
• Reassess lipids 4-8 weeks after initiating or adjusting pharmacologic therapy. 1
• Calculate non-HDL-C (total cholesterol minus HDL-C) with a target goal of <130 mg/dL. 1, 2
• Monitor for myopathy if fibrates are added, particularly checking creatine kinase levels at baseline and if symptoms develop. 1
• Once goals are achieved, follow-up every 6-12 months. 1

Critical Pitfalls to Avoid

• Do not ignore secondary causes: Failing to address uncontrolled diabetes, hypothyroidism, or medications can lead to unnecessary pharmacologic treatment. 1
• Do not use gemfibrozil: If fibrate therapy is needed, use fenofibrate rather than gemfibrozil, as gemfibrozil has significantly higher myopathy risk when combined with statins. 1
• Do not use bile acid sequestrants: These are relatively contraindicated when triglycerides are >200 mg/dL. 1
• Do not delay lifestyle modifications: Even if pharmacologic therapy is indicated, lifestyle changes remain essential and can be more effective than medications in some cases. 1, 4
• Do not use over-the-counter fish oil as a substitute: Over-the-counter supplements are not equivalent to prescription omega-3 formulations. 1

Special Considerations

• For patients with diabetes: Optimizing glycemic control is crucial, as poor glucose control is often the primary driver of hypertriglyceridemia. 1, 7
• For elderly patients: Dose selection should be based on renal function; start fenofibrate at 54 mg daily if mild to moderate renal impairment is present. 3
• If combining fibrate with statin: Use lower statin doses (atorvastatin 10-20 mg maximum) to minimize myopathy risk, particularly in patients >65 years or with renal disease. 1