What is the recommended approach to managing dyslipidemia, including lifestyle changes, risk assessment, and medication selection?

Management of Dyslipidemia

All adults with dyslipidemia should undergo cardiovascular risk stratification using the 10-year ASCVD risk calculator, and those with risk ≥7.5%, diabetes, established CVD, LDL-C ≥190 mg/dL, or chronic kidney disease should immediately start statin therapy alongside intensive lifestyle modifications, targeting LDL-C <100 mg/dL (or <70 mg/dL in very high-risk patients). 1, 2

Risk Assessment and Stratification

Begin by calculating the 10-year ASCVD risk using age, sex, blood pressure, smoking status, and diabetes status. 2 This determines treatment intensity and LDL-C targets:

• Very high-risk patients (established CVD, diabetes with additional risk factors, LDL-C ≥190 mg/dL, chronic kidney disease): Start high-intensity statin immediately, target LDL-C <70 mg/dL 3, 1, 2
• High-risk patients (10-year ASCVD risk ≥7.5%, diabetes age 40-75 years): Start moderate-to-high intensity statin, target LDL-C <100 mg/dL 3, 1, 2
• Moderate-risk patients (10-year ASCVD risk 5-7.5% with risk modifiers): Start moderate-intensity statin, target LDL-C <100 mg/dL 2
• Lower-risk patients (0-1 risk factors): Target LDL-C <160 mg/dL, consider drug therapy only if LDL-C ≥190 mg/dL after 6-12 months of lifestyle modification 1

Critical pitfall: Do not delay statin therapy in diabetic patients with LDL-C >130 mg/dL while attempting prolonged lifestyle modification alone—this wastes time in high-risk patients. 2

Immediate Lifestyle Modifications

Initiate these simultaneously with statin therapy, not sequentially:

• Dietary fat modification: Restrict saturated fat to <7% of total calories, eliminate trans fats to <1%, limit dietary cholesterol to <200 mg/day (achieves 15-25 mg/dL LDL-C reduction) 1, 4
• Add functional foods: Plant stanols/sterols 2 g/day (6-15% additional LDL-C reduction), soluble fiber 10-25 g/day from oats, beans, vegetables (5-10% LDL-C reduction) 1, 5
• Physical activity: 150 minutes/week moderate-intensity aerobic activity or 75 minutes/week vigorous activity, plus resistance training 2 days/week 1
• Weight loss: 5-10% weight loss in overweight patients significantly improves all lipid parameters 4, 6
• Sodium restriction: Particularly important if hypertension coexists 3

The Mediterranean dietary pattern has the strongest cardiovascular outcome evidence among dietary interventions. 5, 6

Statin Selection and Dosing

First-line pharmacotherapy is always a statin unless contraindicated. 3

High-Intensity Statin Options (≥50% LDL-C reduction):

• Atorvastatin 40-80 mg daily: Provides 50% LDL-C reduction 1
• Rosuvastatin 20-40 mg daily: Provides 52-63% LDL-C reduction 1, 7

Moderate-Intensity Statin Options (30-50% LDL-C reduction):

• Atorvastatin 10-20 mg daily: Provides 37-43% LDL-C reduction 1
• Rosuvastatin 5-10 mg daily: Provides 39-45% LDL-C reduction 1

Dose adjustment for renal impairment: Use standard dosing for eGFR ≥60 mL/min/1.73 m²; reduce doses for eGFR <60 mL/min/1.73 m². 2

Monitoring Strategy

• Initial response check: Recheck fasting lipids 4-8 weeks after starting statin therapy 1
• Dose titration: If LDL-C goal not achieved, increase statin dose or add ezetimibe 10 mg daily 1, 2
• Long-term monitoring: Every 6-12 months once LDL-C goal achieved 1
• Liver enzymes: Check before initiation and when clinically indicated (not routinely) 7
• Safety monitoring: Instruct patients to report immediately any unexplained muscle pain, tenderness, weakness (especially with malaise/fever), or dark urine 1, 7

Adding Non-Statin Therapy

Add ezetimibe 10 mg daily only if LDL-C remains above goal after 3 months on maximally tolerated statin, or if patient cannot tolerate adequate statin doses. 3, 1, 2 Ezetimibe provides an additional 15-25% LDL-C reduction. 3

Consider PCSK9 inhibitors (evolocumab 140 mg every 2 weeks or 420 mg monthly, alirocumab) for very high-risk patients who remain above LDL-C goal despite maximally tolerated statin plus ezetimibe. 3, 8 These agents provide an additional 55-63% LDL-C reduction and have demonstrated cardiovascular event reduction in outcome trials. 8 However, cost is prohibitive and availability limited in many regions. 3

Avoid fibrates for isolated LDL-C elevation—they are indicated for triglycerides ≥500 mg/dL or mixed dyslipidemia with low HDL-C. 1 Combination statin-fibrate therapy increases myopathy risk and lacks cardiovascular outcome data. 3, 9

Management of Hypertriglyceridemia

For elevated triglycerides (>150 mg/dL) with low HDL-C:

• Primary intervention: Weight management, reduce simple sugars, increase physical activity 3
• Screen for secondary causes: Diabetes, hypothyroidism, renal disease, alcohol abuse 3
• Pharmacotherapy threshold: Consider fibrate monotherapy only if TG ≥400 mg/dL to prevent pancreatitis risk (TG >1000 mg/dL) 3
• Target levels: TG <150 mg/dL, HDL-C >40 mg/dL (>50 mg/dL in women) 3

Special Populations

Diabetes Mellitus:

All diabetic patients age 40-75 years require at least moderate-intensity statin therapy regardless of baseline LDL-C. 3, 2 Target LDL-C <100 mg/dL, or <70 mg/dL if established CVD. 3 Non-HDL-C goal is <130 mg/dL when triglycerides 200-499 mg/dL. 3

Chronic Kidney Disease/Nephrotic Syndrome:

Consider statin therapy for persistent dyslipidemia, particularly with other cardiovascular risk factors. 3 Lifestyle modifications remain important. 3 Adjust statin doses for reduced eGFR. 2

Children and Adolescents:

Target LDL-C <160 mg/dL (<130 mg/dL preferred); consider pharmacotherapy if LDL-C ≥190 mg/dL with no other risk factors, or ≥160 mg/dL with risk factors present. 3 Bile acid-binding resins or statins are first-line agents, managed by pediatric lipid specialists. 3

Safety Considerations and Contraindications

Absolute contraindications: Acute liver failure, decompensated cirrhosis, pregnancy, nursing. 3, 7

Common adverse effects:

• Myopathy risk 0.1-0.2%, increases with combination therapy 1
• Transient transaminase elevations in 1.1% of patients 7
• Small increases in HbA1c and fasting glucose (optimize lifestyle measures) 7
• Immune-mediated necrotizing myopathy (rare, requires immunosuppression) 7

Management of statin intolerance: Try different statin, reduce dose, alternate-day dosing, or switch to ezetimibe monotherapy if statins cannot be tolerated. 3

Expected Outcomes

With atorvastatin 20-40 mg daily plus lifestyle modifications, expect:

• LDL-C reduction: 43-50% 1
• Triglyceride reduction: 10-30% if elevated 1
• Cardiovascular risk reduction: 25-35% over 5 years in primary prevention populations 1

The combination of high-intensity statin therapy with comprehensive lifestyle modification provides maximal benefit for reducing atherosclerotic cardiovascular disease morbidity and mortality. 3, 1, 8