How should I evaluate and manage an adult with dyslipidemia, including risk assessment, statin therapy selection, lifestyle modifications, and follow‑up?

Evaluation and Management of Adult Dyslipidemia

Initial Risk Assessment and Lipid Screening

Obtain a fasting lipid panel (total cholesterol, LDL-C, HDL-C, triglycerides) at baseline before initiating therapy, then repeat 4-12 weeks after starting or adjusting treatment, and every 3-12 months thereafter for monitoring adherence and therapeutic response. 1

• Fasting lipids are preferred for initial assessment, though non-fasting panels are acceptable for screening when fasting is impractical 2, 3
• Calculate 10-year ASCVD risk using the pooled cohort equations for patients 40-75 years without clinical ASCVD or diabetes 1
• Evaluate for secondary causes of dyslipidemia before initiating therapy: uncontrolled diabetes, hypothyroidism, chronic kidney disease, nephrotic syndrome, liver disease, excessive alcohol intake, and medications (thiazides, beta-blockers, estrogen, corticosteroids, antiretrovirals, antipsychotics) 1, 4

Statin Therapy Selection by Patient Category

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

Initiate high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) for the following groups: 1

• Clinical ASCVD (acute coronary syndrome, MI, stable/unstable angina, coronary revascularization, stroke, TIA, peripheral arterial disease) in patients <75 years 1
• LDL-C ≥190 mg/dL (primary severe hypercholesterolemia) 1
• Diabetes mellitus age 40-75 years with LDL-C 70-189 mg/dL and 10-year ASCVD risk ≥7.5% 1

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

Initiate moderate-intensity statin therapy (atorvastatin 10-20 mg, rosuvastatin 5-10 mg, simvastatin 20-40 mg, pravastatin 40-80 mg) for: 1

• Diabetes mellitus age 40-75 years with LDL-C 70-189 mg/dL without additional ASCVD risk factors 1
• Primary prevention patients age 40-75 years with LDL-C 70-189 mg/dL and 10-year ASCVD risk ≥7.5% 1
• Clinical ASCVD in patients ≥75 years (or high-intensity if tolerated) 1

Risk-Based Discussion for Borderline Risk

For patients age 40-75 years with 10-year ASCVD risk 5-7.5%, engage in clinician-patient discussion regarding statin initiation, particularly if risk-enhancing factors are present (persistently elevated triglycerides ≥175 mg/dL, family history of premature ASCVD, chronic kidney disease, metabolic syndrome, inflammatory conditions). 1

Lifestyle Modifications (Implement Concurrently with Pharmacotherapy)

All patients with dyslipidemia require intensive lifestyle interventions regardless of medication use: 1, 5

Dietary Interventions

• Restrict saturated fat to <7% of total calories (reduces LDL-C by 11-13 mg/dL) 5
• Eliminate trans fats completely (<1% of calories) 5
• Limit dietary cholesterol to <200 mg/day 1
• Add 10-25 grams soluble fiber daily (provides 5-10% additional LDL-C reduction) 5
• Add 2 grams plant stanols/sterols daily (provides 10% additional LDL-C reduction) 5
• Replace saturated fats with polyunsaturated fats (reduces LDL by 1.8 mg/dL per 1% energy substitution) or monounsaturated fats (reduces LDL by 1.3 mg/dL per 1% energy substitution) 5

Physical Activity and Weight Management

• Engage in ≥150 minutes/week moderate-intensity aerobic activity or 75 minutes/week vigorous activity 1, 5
• Target 5-10% weight loss if overweight (produces 20% triglyceride reduction) 6
• Smoking cessation is mandatory 1

Management of Hypertriglyceridemia

Severe to Very Severe Hypertriglyceridemia (≥500 mg/dL)

Initiate fenofibrate 54-160 mg daily immediately as first-line therapy to prevent acute pancreatitis, regardless of LDL-C levels or cardiovascular risk. 1, 6

• Implement extreme dietary fat restriction (10-25% of total calories for 500-999 mg/dL; <10-15% for ≥1000 mg/dL) 6
• Eliminate all added sugars and alcohol completely 6
• Aggressively optimize glycemic control in diabetic patients (can reduce triglycerides by 20-50% independent of medications) 6
• Monitor renal function at baseline, 3 months, then every 6 months; discontinue if eGFR persistently <30 mL/min/1.73 m² 1
• Once triglycerides fall <500 mg/dL, reassess LDL-C and add statin therapy if elevated or cardiovascular risk is high 6

Moderate Hypertriglyceridemia (200-499 mg/dL)

For patients with elevated LDL-C or 10-year ASCVD risk ≥7.5%, initiate moderate-to-high intensity statin therapy as first-line (provides 10-30% triglyceride reduction plus proven cardiovascular benefit). 6

• Target non-HDL-C <130 mg/dL as secondary goal 1, 6
• If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle and statin therapy, consider adding icosapent ethyl 2g twice daily for patients with established ASCVD or diabetes with ≥2 additional risk factors (provides 25% reduction in major adverse cardiovascular events) 6
• Alternative: add fenofibrate 54-160 mg daily if icosapent ethyl criteria not met 6

Mild Hypertriglyceridemia (150-199 mg/dL)

Prioritize aggressive lifestyle modifications for 3 months; consider statin therapy if 10-year ASCVD risk ≥7.5% or persistently elevated triglycerides ≥175 mg/dL serve as risk-enhancing factor. 6

Monitoring Statin Therapy and Optimizing Response

Expected LDL-C Reduction by Statin Intensity

• High-intensity statins: ≥50% LDL-C reduction from baseline 1
• Moderate-intensity statins: 30-<50% LDL-C reduction from baseline 1
• Use these benchmarks to assess adherence, not as performance standards 1

Addressing Insufficient Response

If less-than-anticipated therapeutic response occurs on recommended statin intensity: 1

1. Reinforce medication adherence 1
2. Reinforce intensive lifestyle changes 1
3. Exclude secondary causes of hyperlipidemia 1
4. Titrate to maximum tolerated statin intensity 1

Adding Non-Statin Therapy

For higher-risk individuals (clinical ASCVD <75 years, LDL-C ≥190 mg/dL, diabetes age 40-75 years) on maximum tolerated statin with insufficient response, consider adding nonstatin therapy only if ASCVD risk-reduction benefits outweigh adverse effects: 1

• Ezetimibe 10 mg daily (provides additional 13-20% LDL-C reduction) if LDL-C remains ≥70 mg/dL 7
• Preference should be given to nonstatin drugs shown to reduce ASCVD events in randomized controlled trials 1

Safety Monitoring and Adverse Effects

Myopathy and Rhabdomyolysis Risk Factors

• Age ≥65 years, uncontrolled hypothyroidism, renal impairment, concomitant use with certain drugs (fibrates, cyclosporine, HIV protease inhibitors), higher statin doses 8
• Instruct patients to report immediately: unexplained muscle pain, tenderness, weakness, particularly if accompanied by malaise, fever, or dark urine 8
• Discontinue statin if markedly elevated CK levels occur or myopathy is diagnosed 8

Hepatic Monitoring

• Consider baseline liver enzymes before initiating therapy 1, 8
• If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia occurs, promptly discontinue statin 8

Combination Therapy Precautions

• When combining fenofibrate with statins, use fenofibrate (NOT gemfibrozil) and lower statin doses to minimize myopathy risk, particularly in patients >65 years or with renal disease 6
• Monitor creatine kinase levels and muscle symptoms when using combination therapy 6

Special Populations

Diabetes Mellitus

• All diabetic patients age 40-75 years should receive at least moderate-intensity statin therapy regardless of baseline LDL-C 1
• Target LDL-C <100 mg/dL (or <70 mg/dL for very high-risk patients) 1
• Optimize glycemic control as priority for severe hypertriglyceridemia 6

Elderly (≥75 years)

• Continue moderate-intensity statin for clinical ASCVD; consider high-intensity if tolerated 1
• Increased myopathy risk with combination therapy requires careful monitoring 6

Pediatric Patients (≥10 years) with Familial Hypercholesterolemia

• Heterozygous FH: start atorvastatin 10 mg daily, range 10-20 mg daily 8
• Homozygous FH: start atorvastatin 10-20 mg daily, range 10-80 mg daily 8

Common Pitfalls to Avoid

• Do not delay statin therapy while attempting lifestyle modifications alone in high-risk patients (diabetes, 10-year ASCVD risk ≥7.5%, clinical ASCVD)—pharmacotherapy and lifestyle optimization should occur simultaneously 6, 7
• Do not start with statin monotherapy when triglycerides ≥500 mg/dL—fibrates must be initiated first to prevent pancreatitis 6
• Do not use gemfibrozil when combining with statins—fenofibrate has significantly better safety profile 6
• Do not add nonstatin therapy before maximizing statin intensity in appropriate candidates 1
• Do not overlook secondary causes of dyslipidemia (uncontrolled diabetes, hypothyroidism, medications, alcohol)—addressing these can dramatically improve lipid levels 1, 4