What is the treatment for elevated cholesterol and triglycerides?

Treatment of Elevated Cholesterol and Triglycerides

Initial Assessment and Risk Stratification

Before initiating treatment, evaluate for secondary causes including uncontrolled diabetes mellitus, hypothyroidism, excessive alcohol intake, medications (thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, antipsychotics), and renal or liver disease. 1

• Assess cardiovascular risk factors including family history, central obesity, hypertension, and abnormal glucose metabolism 1
• Classify triglyceride severity: Normal <150 mg/dL, Mild 150-199 mg/dL, Moderate 200-499 mg/dL, Severe 500-999 mg/dL, Very severe ≥1000 mg/dL 2
• Determine 10-year ASCVD risk to guide pharmacologic therapy decisions 2

Therapeutic Lifestyle Changes

Lifestyle modifications are the foundation of treatment and can reduce LDL-C by 20-30% and triglycerides by 20-70%. 1, 3

Dietary Modifications for Elevated LDL Cholesterol

• Restrict saturated fat to <7% of total calories 1
• Limit dietary cholesterol to <200 mg/day 1
• Eliminate trans fats to <1% of calories 1
• Add plant stanols/sterols 2 g/day (reduces LDL-C by 8-29 mg/dL) 1
• Increase soluble fiber to 10-25 g/day (reduces LDL-C by ~2.2 mg/dL per gram) 1

Dietary Modifications for Elevated Triglycerides (Severity-Based)

For mild-moderate hypertriglyceridemia (150-499 mg/dL):

• Restrict added sugars to <6% of total daily calories 1, 2
• Limit total fat to 30-35% of total daily calories 1, 2
• Consume ≥2 servings (8+ ounces) per week of fatty fish rich in omega-3 fatty acids 2

For severe hypertriglyceridemia (500-999 mg/dL):

• Restrict dietary fat to 20-25% of total calories 1, 2
• Eliminate all added sugars completely 1, 2
• Complete abstinence from alcohol 2

For very severe hypertriglyceridemia (≥1000 mg/dL):

• Implement very low-fat diet (10-15% of total calories) 1, 2
• In some cases, consider extreme dietary fat restriction (<5% of total calories) until triglycerides are ≤1000 mg/dL 2

Physical Activity and Weight Loss

• Engage in at least 150 minutes/week of moderate-intensity or 75 minutes/week of vigorous aerobic activity 2
• Target 5-10% weight loss, which produces a 20% decrease in triglycerides 2
• In some patients, weight loss can reduce triglyceride levels by up to 70% 2

Pharmacologic Treatment Algorithm

For Elevated LDL Cholesterol

Statin therapy is first-line treatment for elevated LDL cholesterol, with a goal of reducing LDL-C to <100 mg/dL for patients with CHD or CHD equivalents. 1

• Initiate moderate-to-high intensity statin therapy based on ASCVD risk 1
• High-intensity statins (atorvastatin 40-80 mg, rosuvastatin 20-40 mg) provide ≥50% LDL-C reduction 2
• Statins also provide 10-30% dose-dependent reduction in triglycerides 2

For Elevated Triglycerides (Treatment Algorithm by Level)

For triglycerides ≥500 mg/dL:

• Initiate fenofibrate 54-200 mg daily immediately to prevent acute pancreatitis, before addressing LDL cholesterol 1, 2, 4
• Fenofibrate reduces triglycerides by 30-50% 2, 4
• Once triglycerides fall below 500 mg/dL, reassess LDL-C and add statin therapy if LDL-C is elevated or cardiovascular risk is high 2

For triglycerides 200-499 mg/dL:

• If LDL-C is elevated or ASCVD risk ≥7.5%, initiate or optimize statin therapy as first-line 1, 2
• Target non-HDL-C <130 mg/dL 2
• If triglycerides remain elevated >200 mg/dL after 3 months of optimized lifestyle and statin therapy, add prescription omega-3 fatty acids (icosapent ethyl) 2-4 g/day 1, 2

For triglycerides 150-199 mg/dL:

• If persistently elevated nonfasting triglycerides ≥175 mg/dL with ASCVD risk 7.5% to <20%, consider initiating at least moderate-intensity statin therapy 2
• If ASCVD risk is 5% to <7.5%, engage in patient-clinician discussion regarding statin initiation 2

Prescription Omega-3 Fatty Acids (Icosapent Ethyl)

Icosapent ethyl is indicated as adjunct to maximally tolerated statin therapy for patients with triglycerides ≥150 mg/dL and established cardiovascular disease OR diabetes with ≥2 additional risk factors. 2

• Dose: 2-4 g/day 1, 2
• Provides 25% reduction in major adverse cardiovascular events (REDUCE-IT trial) 2
• Monitor for increased risk of atrial fibrillation 2

Special Populations

Diabetic Patients

Optimize glycemic control as the highest priority, with target HbA1c <7%, as poor glucose control is often the primary driver of severe hypertriglyceridemia. 1, 2

• Aggressively optimizing glycemic control can dramatically reduce triglycerides independent of lipid medications 2
• Consider metformin for patients with impaired glucose regulation 2

Patients with Metabolic Syndrome

• Prioritize improved glycemic control, modest weight loss, dietary saturated fat restriction, increased physical activity, and incorporation of monounsaturated fats 1

Combination Therapy Considerations

When combining fenofibrate with statins, use lower statin doses (atorvastatin 10-20 mg maximum) to minimize myopathy risk, particularly in patients >65 years or with renal disease. 2

• Fenofibrate has a better safety profile than gemfibrozil when combined with statins 2
• Monitor creatine kinase levels and muscle symptoms when using combination therapy 2
• The ACCORD trial showed no cardiovascular benefit from adding fenofibrate to statins in diabetic patients, but fenofibrate remains indicated for severe hypertriglyceridemia to prevent pancreatitis 2

Monitoring Strategy

• Reassess fasting lipid panel 4-8 weeks after initiating or adjusting therapy 1
• Monitor liver enzymes and myopathy symptoms as clinically indicated 1
• Once goals are achieved, follow-up every 6-12 months 2

Critical Pitfalls to Avoid

• Do not delay fibrate initiation while attempting lifestyle modifications alone in patients with triglycerides ≥500 mg/dL—pharmacologic therapy is mandatory to prevent pancreatitis 2
• Do not start with statin monotherapy when triglycerides are ≥500 mg/dL—initiate fibrates before LDL-lowering therapy 2
• Do not use bile acid sequestrants when triglycerides are >200 mg/dL (relatively contraindicated) 2
• Do not substitute over-the-counter fish oil supplements for prescription omega-3 formulations 2
• Do not overlook secondary causes, particularly uncontrolled diabetes and hypothyroidism, which may be more effectively treated than adding additional lipid medications 1, 2