Management of Triglycerides at 220 mg/dL
For a fasting triglyceride level of 220 mg/dL, you should implement aggressive lifestyle modifications immediately and initiate moderate-to-high intensity statin therapy if the patient has a 10-year ASCVD risk ≥7.5%, diabetes (age 40-75), or established cardiovascular disease—do not delay pharmacotherapy while pursuing lifestyle changes alone in these high-risk groups. 1, 2
Classification and Risk Assessment
A triglyceride level of 220 mg/dL falls into moderate hypertriglyceridemia (200-499 mg/dL), which is associated with increased cardiovascular risk through atherogenic VLDL remnant particles but remains well below the 500 mg/dL threshold that mandates immediate fibrate therapy for pancreatitis prevention. 1, 2 This level constitutes a cardiovascular risk-enhancing factor that should influence treatment intensity decisions. 1
The primary concern at this level is long-term cardiovascular disease risk, not acute pancreatitis. 1, 3 Calculate the patient's 10-year ASCVD risk using the Pooled Cohort Equations to determine the need for pharmacologic therapy beyond lifestyle measures. 1, 4
Evaluation for Secondary Causes (First Step)
Before initiating any triglyceride-lowering therapy, systematically screen for reversible contributors—addressing these can lower triglycerides by 20-50% independent of pharmacotherapy: 1
Check HbA1c and fasting glucose: Uncontrolled diabetes is often the primary driver of hypertriglyceridemia; optimizing glycemic control can reduce triglycerides by 20-50% without additional lipid medications. 1, 5
Measure TSH: Hypothyroidism must be excluded and treated before expecting a full lipid-lowering response. 1
Obtain detailed alcohol history: Even modest intake (≈1 oz daily) raises triglycerides by 5-10%, and the effect is amplified when combined with high saturated-fat meals. 1 Complete abstinence may be required as levels approach 500 mg/dL. 1
Review medications: Discontinue or substitute agents that raise triglycerides when possible—thiazide diuretics, beta-blockers, oral estrogen, corticosteroids, antiretrovirals, and atypical antipsychotics. 1
Assess renal and hepatic function: Chronic kidney or liver disease contributes to hypertriglyceridemia and influences drug selection and dosing. 1
Lifestyle Interventions (Foundational for All Patients)
Intensive lifestyle changes can lower triglycerides by 20-70% and should be instituted immediately alongside any pharmacotherapy in high-risk patients: 1
Weight Management
- Target a 5-10% body-weight reduction, which yields an approximate 20% decrease in triglycerides—this is the single most effective lifestyle measure. 1, 6 In some individuals, weight loss alone can achieve 50-70% triglyceride reduction. 1
Dietary Modifications
Restrict added sugars to <6% of total daily calories (≈30 g on a 2,000-kcal diet) to curb hepatic triglyceride synthesis. 1
Limit total dietary fat to 30-35% of calories for moderate hypertriglyceridemia. 1
Restrict saturated fat to <7% of calories and replace with monounsaturated or polyunsaturated fats (olive oil, nuts, avocado, fatty fish). 1, 3
Eliminate trans fats completely—they raise triglycerides and atherogenic lipoproteins. 1
Increase soluble fiber to >10 g/day from oats, beans, lentils, and vegetables. 1
Consume ≥2 servings/week of fatty fish (salmon, trout, sardines, mackerel) to provide dietary omega-3 fatty acids. 1
Physical Activity
- Engage in ≥150 minutes/week of moderate-intensity aerobic exercise (or 75 minutes/week vigorous), which reduces triglycerides by approximately 11%. 1, 4
Alcohol Restriction
- Limit or avoid alcohol; even modest intake raises triglycerides by 5-10%, especially when levels are near 500 mg/dL. 1
Pharmacologic Therapy Decision Algorithm
High-Risk Patients (Statin Therapy Indicated)
Initiate moderate-to-high intensity statin therapy immediately when any of the following are present: 1, 2
- 10-year ASCVD risk ≥7.5%
- Diabetes mellitus (age 40-75 years)
- Established ASCVD
- LDL-C ≥190 mg/dL
Do not delay statin initiation while pursuing lifestyle changes—both should start concurrently in high-risk patients. 1
Recommended Statin Regimens
Atorvastatin 10-20 mg daily or rosuvastatin 5-10 mg daily (moderate-to-high intensity). 1
Statins provide a dose-dependent 10-30% reduction in triglycerides in addition to proven cardiovascular mortality benefit via LDL-C lowering. 1, 3
Lipid Targets While on Statin Therapy
- LDL-C <100 mg/dL (or <70 mg/dL for very high-risk patients) 1
- Non-HDL-C <130 mg/dL 1, 3
- Triglycerides <200 mg/dL (ideally <150 mg/dL) 1
Lower-Risk Patients
For individuals with 10-year ASCVD risk <7.5% and no diabetes or established ASCVD: 1
Prioritize intensive lifestyle modification for at least 3 months before considering pharmacotherapy. 1
Re-measure fasting lipid panel 6-12 weeks after lifestyle implementation. 1
Consider a moderate-intensity statin after shared decision-making if risk-enhancing factors are present (family history of premature ASCVD, chronic kidney disease, metabolic syndrome, triglycerides ≥175 mg/dL). 1
Add-On Therapy When Triglycerides Remain >200 mg/dL After 3 Months
If triglycerides stay above 200 mg/dL after ≥3 months of optimized lifestyle modifications and statin therapy, consider the following: 1
Icosapent Ethyl (Prescription EPA) – Preferred Add-On
Add icosapent ethyl 2 g twice daily (total 4 g/day) for patients with: 1
- Established cardiovascular disease OR
- Diabetes plus ≥2 additional cardiovascular risk factors (e.g., hypertension, smoking, family history, age >50 y men/ >60 y women, chronic kidney disease)
Evidence: The REDUCE-IT trial demonstrated a 25% relative risk reduction in major adverse cardiovascular events (NNT = 21 over 4.9 years)—this is Level A evidence from a large randomized controlled trial. 1, 4
Icosapent ethyl is the only triglyceride-lowering agent FDA-approved for cardiovascular risk reduction. 1
Safety: Monitor for a modest increase in atrial fibrillation (3.1% vs 2.1% with placebo). 1
Fenofibrate – Alternative Add-On
Add fenofibrate 54-160 mg daily if: 1, 2
- Triglycerides remain >200 mg/dL after 3 months of optimized lifestyle and statin therapy AND
- The patient does not meet icosapent ethyl criteria
Efficacy: Produces a 30-50% triglyceride reduction. 1, 7
- Use fenofibrate (not gemfibrozil) because it does not inhibit statin glucuronidation and has a superior safety profile.
- Consider lower statin doses (atorvastatin ≤20 mg or rosuvastatin ≤10 mg) in patients >65 years or with renal impairment to minimize myopathy risk.
Evidence limitation: The ACCORD trial demonstrated no cardiovascular event reduction when fenofibrate was added to simvastatin in diabetics; fenofibrate's role is limited to triglyceride lowering. 1, 2
Monitoring Strategy
Calculate non-HDL-C (total cholesterol – HDL-C) and aim for <130 mg/dL as a secondary target when triglycerides are elevated. 1, 3
Re-assess fasting lipid panel: 1
- 6-12 weeks after lifestyle changes
- 4-8 weeks after initiating or adjusting statin therapy
- 4-8 weeks after adding fenofibrate or icosapent ethyl
If fenofibrate is added: 1
- Obtain baseline and follow-up creatine kinase levels
- Monitor for muscle symptoms
- Check renal function at baseline, 3 months, then every 6 months
Treatment Goals
Primary: Reduce triglycerides to <200 mg/dL (ideally <150 mg/dL) to lower cardiovascular risk. 1
Tertiary: Attain LDL-C <100 mg/dL (or <70 mg/dL for very high-risk patients). 1
Critical Pitfalls to Avoid
Do not postpone statin initiation while attempting lifestyle changes alone in high-risk patients (ASCVD risk ≥7.5%, diabetes, established ASCVD)—both should be started concurrently. 1, 2
Do not overlook secondary causes (uncontrolled diabetes, hypothyroidism, excess alcohol, offending medications)—correcting these can lower triglycerides by 20-50% and may obviate the need for additional lipid agents. 1
Do not start fenofibrate at a triglyceride level of 220 mg/dL in high-risk patients—statins are first-line for moderate hypertriglyceridemia when cardiovascular risk is elevated. 1, 2
Do not combine gemfibrozil with statins—fenofibrate has a markedly better safety profile with lower myopathy risk. 1, 2
Do not rely on over-the-counter fish-oil supplements for cardiovascular benefit—only prescription icosapent ethyl has proven outcome data. 1
Do not add fibrates or omega-3 agents before completing at least 3 months of intensive lifestyle and statin therapy (unless triglycerides exceed 500 mg/dL). 1