What are the management strategies for a patient with an elevated Triglyceride (TG) to High-Density Lipoprotein (HDL) ratio?

Management of Elevated Triglyceride to HDL Ratio

For patients with an elevated TG/HDL ratio, prioritize aggressive lifestyle modifications targeting weight loss, sugar elimination, and increased physical activity, while initiating statin therapy if cardiovascular risk is elevated (10-year ASCVD risk ≥7.5%) or if diabetes is present, and consider adding prescription omega-3 fatty acids (icosapent ethyl) or fenofibrate only after optimizing lifestyle changes and statin therapy for 3 months if triglycerides remain >200 mg/dL. 1, 2

Understanding the TG/HDL Ratio as a Risk Marker

The TG/HDL ratio serves as a simple surrogate marker for insulin resistance and increased cardiometabolic risk, with sex-specific cutpoints of ≥3.0 for men and ≥2.0 for women identifying the highest-risk quartile. 3, 4 An elevated ratio predicts long-term all-cause mortality and major adverse cardiac events independent of traditional cardiovascular risk factors, with a TG/HDL ratio ≥2.5 conferring a 2-fold increased risk of mortality. 5, 6 The ratio also correlates strongly with small, dense LDL particles—a cutoff of 1.33 (using molar concentrations) distinguishes patients with small LDL particles with 90% sensitivity. 7

However, current guidelines do not use the TG/HDL ratio as a treatment target—instead, they focus on absolute triglyceride levels and LDL-C goals. 1 The ratio is best utilized as a screening tool to identify patients who warrant more aggressive cardiovascular risk factor modification.

Lifestyle Modifications: The Foundation of Treatment

Weight Management and Physical Activity

• Target a 5-10% body weight reduction, which produces a 20% decrease in triglycerides—this is the single most effective lifestyle intervention and will simultaneously improve the TG/HDL ratio. 2, 8
• In some patients, weight loss can reduce triglyceride levels by up to 50-70%, making it more effective than many pharmacologic interventions. 2
• 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
• Consider adding resistance training 2-3 times per week for additional cardiovascular benefits. 8

Dietary Interventions

• Restrict added sugars to <6% of total daily calories, as sugar intake directly increases hepatic triglyceride production. 2, 8
• Eliminate all sugar-sweetened beverages completely. 2
• Limit total dietary fat to 30-35% of total calories for mild-moderate hypertriglyceridemia (150-499 mg/dL). 2, 8
• Restrict saturated fats to <7% of total energy intake, replacing with monounsaturated or polyunsaturated fats. 1, 2, 8
• Eliminate trans fatty acids completely, as they increase triglycerides and atherogenic lipoproteins. 2, 8
• Increase soluble fiber to >10 g/day from sources like oats, beans, and vegetables. 2, 8
• Consume at least 2 servings per week of fatty fish (salmon, trout, sardines) rich in omega-3 fatty acids. 1, 2, 8
• Limit or completely avoid alcohol consumption, as even 1 ounce daily increases triglycerides by 5-10%. 1, 2

Pharmacologic Therapy: A Stepwise Approach

Step 1: Assess Cardiovascular Risk and Consider Statin Therapy

Statins should be the first-line pharmacologic intervention for most patients with an elevated TG/HDL ratio who have elevated cardiovascular risk. 1, 2

• For adults 40-75 years with 10-year ASCVD risk ≥7.5%, initiate moderate-to-high intensity statin therapy (atorvastatin 20-40 mg or rosuvastatin 10-20 mg daily). 2
• For patients with diabetes aged 40-75 years, initiate statin therapy regardless of baseline LDL levels, as diabetes itself is a high-risk condition. 2
• Statins provide 10-30% dose-dependent triglyceride reduction in addition to proven cardiovascular benefit. 2, 9
• If 10-year ASCVD risk is 5% to <7.5%, engage in a patient-clinician discussion regarding statin initiation, as persistently elevated triglycerides ≥175 mg/dL constitute a cardiovascular risk-enhancing factor. 2

Step 2: Reassess After 3 Months of Optimized Lifestyle and Statin Therapy

• Recheck fasting lipid panel in 6-12 weeks after implementing lifestyle modifications. 2, 8
• Reassess lipids 4-8 weeks after initiating or adjusting statin therapy. 2, 8
• Calculate non-HDL-C (total cholesterol minus HDL-C) with a target goal of <130 mg/dL for patients with triglycerides 200-499 mg/dL. 1, 2

Step 3: Consider Add-On Therapy if Triglycerides Remain >200 mg/dL

If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, consider adding prescription omega-3 fatty acids (icosapent ethyl) as first-line adjunctive therapy. 2

Icosapent Ethyl (Prescription Omega-3)

• Icosapent ethyl 2 g twice daily is indicated as adjunct to maximally tolerated statin therapy for patients with triglycerides ≥150 mg/dL who have either established cardiovascular disease OR diabetes with ≥2 additional cardiovascular risk factors. 2
• The REDUCE-IT trial demonstrated a 25% reduction in major adverse cardiovascular events (number needed to treat = 21). 2
• Icosapent ethyl is the only triglyceride-lowering therapy approved by the FDA for cardiovascular risk reduction. 2
• Monitor for increased risk of atrial fibrillation (3.1% hospitalization rate vs. 2.1% on placebo). 2

Fenofibrate as an Alternative

• If icosapent ethyl criteria are not met, consider fenofibrate 54-160 mg daily, which provides 30-50% triglyceride reduction. 2, 9
• Fenofibrate is preferred over gemfibrozil when combining with statins due to significantly lower myopathy risk. 2
• When combining fenofibrate with statins, use lower statin doses to minimize myopathy risk, particularly in patients >65 years or with renal disease. 2
• Monitor creatine kinase levels and muscle symptoms, especially at baseline and 3 months after initiation. 2

Special Considerations for Severe Hypertriglyceridemia (≥500 mg/dL)

If triglycerides reach ≥500 mg/dL, immediate pharmacologic intervention with fenofibrate is mandatory to prevent acute pancreatitis, regardless of the TG/HDL ratio. 1, 2

• Initiate fenofibrate 54-160 mg daily immediately as first-line therapy, before addressing LDL cholesterol. 2
• Restrict total dietary fat to 20-25% of total daily calories for triglycerides in the 500-999 mg/dL range. 2
• Eliminate all added sugars completely and abstain from all alcohol consumption. 2
• Once triglycerides fall below 500 mg/dL, reassess LDL-C and consider adding or optimizing statin therapy. 2

Common Pitfalls to Avoid

• Do not delay statin therapy while attempting lifestyle modifications alone in patients with elevated cardiovascular risk—pharmacologic intervention should occur simultaneously with lifestyle changes, not sequentially. 2
• Do not use the TG/HDL ratio as a treatment target—focus on absolute triglyceride levels (<150 mg/dL ideally, <200 mg/dL minimum) and LDL-C goals (<100 mg/dL for high-risk patients). 1, 2
• Do not start with fibrate monotherapy unless triglycerides are ≥500 mg/dL or the patient has a statin contraindication—statins provide proven cardiovascular benefit and should be first-line for most patients. 2
• Do not combine high-dose statins with fibrates without careful consideration, as this significantly increases myopathy risk—use lower statin doses when combining. 2
• Do not use over-the-counter fish oil supplements as a substitute for prescription omega-3 formulations, as they are not equivalent and lack proven cardiovascular benefit. 2
• Do not ignore secondary causes of hypertriglyceridemia, including uncontrolled diabetes, hypothyroidism, excessive alcohol intake, and certain medications (thiazides, beta-blockers, estrogen, corticosteroids). 2

Monitoring Strategy

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications. 2, 8
• Recheck lipids 4-8 weeks after initiating or adjusting pharmacologic therapy. 2, 8
• Monitor liver function tests (ALT/AST) at baseline and periodically, especially if transaminases are elevated. 8
• Monitor for muscle symptoms and consider baseline and follow-up creatine kinase levels if symptoms develop. 8
• Once goals are achieved, follow-up every 6-12 months. 2