How to evaluate and treat hyperlipidemia?

Evaluation and Treatment of Hyperlipidemia

Initial Evaluation

Begin lipid screening with a fasting lipid panel that includes total cholesterol, LDL-C, HDL-C, and triglycerides to establish baseline values and guide treatment decisions. 1

Screening Frequency

• Adults: Obtain lipid testing at least annually, or every 2 years if low-risk values are present (LDL <100 mg/dL, HDL >60 mg/dL, triglycerides <150 mg/dL) 2
• Children with diabetes: Perform lipid profile after diagnosis once glycemic control is achieved, then every 5 years if low-risk 2
• Adults with diabetes: Test annually or more frequently if needed to achieve goals 2

Risk Stratification

Assess cardiovascular risk by evaluating:

• Established CHD or CHD risk equivalents (diabetes, other atherosclerotic disease, or 10-year CHD risk ≥20%) 2
• Major risk factors: Cigarette smoking, hypertension (BP ≥140 mmHg or on medication), low HDL-C (<40 mg/dL), family history of premature CHD, age (men >45 years, women >55 years) 2
• Calculate 10-year CHD risk for patients without established disease to determine treatment intensity 2

Treatment Goals Based on Risk Category

Target LDL-C <100 mg/dL for patients with diabetes or CHD risk equivalents, and <70 mg/dL for highest-risk patients with established cardiovascular disease. 1, 2

LDL-C Goals by Risk Category

• Highest risk (established CVD): LDL <55-70 mg/dL 1, 2
• CHD or CHD risk equivalent: LDL <100 mg/dL 2, 1
• 2+ risk factors with 10-year risk 10-20%: LDL <130 mg/dL 2
• 0-1 risk factors: LDL <160 mg/dL 2

Additional Lipid Targets

• HDL-C: >40 mg/dL (men), >50 mg/dL (women); >35 mg/dL in children with diabetes 2
• Triglycerides: <150 mg/dL (optimal); <200 mg/dL (acceptable) 2
• Non-HDL-C (when triglycerides 200-500 mg/dL): 30 mg/dL higher than LDL-C goal 2

Lifestyle Modifications (Therapeutic Lifestyle Changes)

All patients must implement dietary changes and exercise before or concurrent with pharmacotherapy, as these interventions form the foundation of hyperlipidemia management. 1, 3

Dietary Interventions

• Saturated fat: Reduce to <7% of total calories 2, 1
• Dietary cholesterol: Limit to <200 mg/day 2, 1
• Trans fats: Eliminate completely 1
• Monounsaturated fats: Aim for <10% of calories 2
• Add plant stanols/sterols (2 g/day) and viscous fiber to enhance LDL lowering 1
• For hypertriglyceridemia: Decrease simple sugars, increase dietary omega-3 fatty acids 2

Physical Activity

• Aerobic exercise: At least 30 minutes of moderate-intensity activity most days of the week 1
• Resistance training: 2 days per week 1
• Regular physical activity raises HDL-C by 10-13% when combined with diet and weight loss 4

Other Lifestyle Factors

• Weight loss: Critical for patients with metabolic syndrome and hypertriglyceridemia 2
• Smoking cessation: Can increase HDL-C up to 30% 2, 1
• Alcohol: Abstinence recommended for hypertriglyceridemia; moderate consumption may raise HDL-C 2

Pharmacological Treatment

Statins are first-line pharmacotherapy for LDL-C lowering and should be initiated when lifestyle modifications fail to achieve target LDL levels after an adequate trial period. 2, 1

When to Initiate Drug Therapy

Thresholds for Starting Statins:

• CHD or CHD risk equivalent: Start at LDL ≥130 mg/dL (consider at 100-129 mg/dL) 2
• Diabetes without CVD: Start at LDL ≥130 mg/dL 2, 1
• Established CVD or diabetes with risk factors: Initiate regardless of baseline LDL 1
• Children with diabetes: Start statin if LDL remains >130 mg/dL after 6 months of dietary intervention 2

Statin Therapy

• High-potency statins (atorvastatin, rosuvastatin, pitavastatin) are preferred for maximum LDL reduction 1
• Statins lower LDL-C by 30-50% and modestly raise HDL-C 2
• Monitor: Obtain lipid panel 4-12 weeks after initiation, then every 6-12 months once at goal 2, 1
• Safety monitoring: Check liver function tests, creatine kinase, glucose, and creatinine before starting and periodically thereafter 1

Second-Line and Combination Therapy

For patients not achieving LDL goals on statin monotherapy, add ezetimibe as the safest and most effective second-line option. 1

Add-On Therapies (in order of preference):

1. Ezetimibe: Safest combination with statins, further reduces LDL-C 1
2. Fenofibrate: Preferred fibrate over gemfibrozil due to lower rhabdomyolysis risk when combined with statins 1, 5
3. Bile acid sequestrants: Alternative option but less convenient 2, 1

For Statin-Intolerant Patients:

• Bempedoic acid: Reduces LDL-C by ~23% and cardiovascular events by 13% in statin-intolerant patients 2
• Inclisiran: Maintains 45% LDL-C reduction through 4 years with twice-yearly dosing 2

Treatment of Hypertriglyceridemia

Severe hypertriglyceridemia (≥500 mg/dL) requires immediate intervention to reduce pancreatitis risk, while moderate elevation (175-499 mg/dL) warrants addressing secondary causes and lifestyle factors. 2, 5

Management Strategy:

• First: Optimize glycemic control in diabetic patients, as this often eliminates need for drug therapy 5
• Address secondary causes: Hypothyroidism, liver/kidney disease, medications (estrogen, thiazides, beta-blockers) 5
• Lifestyle: Weight loss, alcohol abstinence, dietary changes 2, 5

Pharmacotherapy for Triglycerides:

• Fenofibrate: 54-160 mg daily with meals; most effective for triglyceride lowering 2, 5
• Icosapent ethyl: Consider adding to statin therapy for patients with controlled LDL but elevated triglycerides (135-499 mg/dL) and ASCVD 2
• Niacin: Most effective for raising HDL-C (up to 35% increase), but may worsen glucose control at high doses 2

Special Considerations for Fenofibrate

• Dosing: Start at 54 mg daily in mild-moderate renal impairment; avoid in severe renal impairment 5
• Administration: Give with meals to optimize bioavailability 5
• Monitoring: Reassess lipids at 4-8 week intervals; discontinue if no adequate response after 2 months at maximum dose 5
• Contraindications: Severe renal impairment, active liver disease, preexisting gallbladder disease, nursing mothers 5

Common Pitfalls and Caveats

• Do not delay statin therapy in high-risk patients waiting for lifestyle changes alone; initiate both simultaneously 1
• Avoid gemfibrozil-statin combinations due to high rhabdomyolysis risk; use fenofibrate instead 1
• Monitor for statin-induced diabetes: Statins slightly increase diabetes risk, but cardiovascular benefits outweigh this risk 2
• Adjust for renal function: Reduce fenofibrate dose in renal impairment and avoid in severe disease 5
• Reassess therapy: If lipid levels fall significantly below target range, consider dose reduction 5
• Non-HDL-C is crucial when triglycerides are 200-500 mg/dL, as LDL-C calculation becomes unreliable 2