What are the steps for diagnosing and managing hyperlipidemia?

Step-by-Step Diagnosis, Management, and Follow-Up of Hyperlipidemia

Diagnosis

Obtain a fasting lipid panel including total cholesterol (TC), LDL-C, HDL-C, and triglycerides as the primary diagnostic test for hyperlipidemia. 1

Initial Laboratory Assessment

• Measure fasting lipid panel (12-hour fast) including TC, LDL-C, HDL-C, and triglycerides 1
• Calculate non-HDL-C (TC minus HDL-C) as a secondary risk marker, particularly important in patients with elevated triglycerides 1
• Use the Friedewald formula to calculate LDL-C: LDL-C = TC - HDL-C - (TG/5) in mg/dL, but only if triglycerides are <400 mg/dL 1
• Obtain at least two separate measurements before making treatment decisions due to intraindividual variability 1

Diagnostic Criteria

• Hypercholesterolemia: LDL-C ≥130 mg/dL 2
• Low HDL-C: <40 mg/dL in men, <50 mg/dL in women 2
• Hypertriglyceridemia classification 1:
  • Mild: 150-199 mg/dL
  • Moderate: 200-999 mg/dL
  • Severe: 1,000-1,999 mg/dL
  • Very severe: ≥2,000 mg/dL

Screen for Secondary Causes

Before initiating treatment, systematically evaluate and address secondary causes of hyperlipidemia. 1

• Evaluate for: excessive alcohol intake, uncontrolled diabetes mellitus, hypothyroidism, renal disease (GFR <60 mL/min/1.73 m²), liver disease, pregnancy, autoimmune disorders 1
• Review medications that can cause dyslipidemia: thiazide diuretics, beta-blockers, estrogen, isotretinoin, corticosteroids, bile acid-binding resins, antiretroviral protease inhibitors, immunosuppressants, antipsychotics 1
• Measure TSH to exclude hypothyroidism 1
• Assess renal function (creatinine, GFR) and liver enzymes (ALT, AST) 1

Identify Familial Hypercholesterolemia

Suspect familial hypercholesterolemia (FH) in patients with LDL-C >190 mg/dL in adults or >150 mg/dL in children, premature CHD (men <55 years, women <60 years), family history of premature CVD, or tendon xanthomas. 1

• Perform family cascade screening when FH is diagnosed in an index case 1
• In children with suspected FH, test from age 5 years or earlier if homozygous FH is suspected 1

Risk Stratification

Use the SCORE system or equivalent cardiovascular risk calculator to stratify patients into very high, high, moderate, or low risk categories. 1

Risk Categories

• Very high risk: Documented CVD, diabetes with target organ damage or multiple risk factors, severe CKD (GFR <30 mL/min/1.73 m²), calculated 10-year risk of CVD death ≥10%, or FH with CVD 1
• High risk: Markedly elevated single risk factors (TC >8 mmol/L or 310 mg/dL), diabetes without target organ damage, moderate CKD (GFR 30-59 mL/min/1.73 m²), or calculated 10-year risk 5-10% 1
• Moderate to low risk: Calculated 10-year risk <5% 1

Additional Risk Assessment

• Assess all cardiovascular risk factors: smoking status, hypertension (BP ≥130/80 mmHg), family history of premature CVD, central obesity (waist circumference ≥94 cm in men, ≥80 cm in women), BMI ≥25 kg/m² 1, 2
• Consider screening patients with autoimmune conditions (rheumatoid arthritis, SLE, psoriasis), peripheral arterial disease, or those on antiretroviral therapy 1

Management

Lifestyle Modifications (All Patients)

Initiate intensive lifestyle modifications immediately in all patients with hyperlipidemia, including dietary changes, weight loss if overweight/obese, increased physical activity, and smoking cessation. 1

• Dietary counseling: Reduce saturated fat intake, increase consumption of olive oil and nuts, reduce simple carbohydrates (especially in hypertriglyceridemia) 1
• Weight loss: Target BMI <25 kg/m² if overweight or obese 1
• Physical activity: Regular aerobic exercise 1
• Smoking cessation: Mandatory counseling and support 1
• Alcohol reduction: Especially critical in hypertriglyceridemia 1

Pharmacological Treatment

The treatment approach and LDL-C goals are determined by cardiovascular risk category. 1

Very High Risk Patients

Initiate high-intensity statin therapy immediately with a goal of LDL-C <70 mg/dL (1.8 mmol/L) or ≥50% reduction from baseline if baseline LDL-C is 70-135 mg/dL. 1

• High-intensity statins: Atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily 1, 3
• Add ezetimibe 10 mg daily if LDL-C goal not achieved with maximally tolerated statin 1
• Consider PCSK9 inhibitors if LDL-C remains elevated despite statin plus ezetimibe 1
• In acute coronary syndrome, initiate or continue high-dose statin early after admission regardless of baseline LDL-C 1

High Risk Patients

Target LDL-C <100 mg/dL (2.6 mmol/L) or ≥50% reduction from baseline if baseline LDL-C is 100-200 mg/dL. 1

• Start with moderate to high-intensity statin (atorvastatin 10-40 mg or rosuvastatin 5-20 mg) 1
• Add ezetimibe if goal not achieved 1

Moderate Risk Patients

• Target LDL-C <115 mg/dL (3.0 mmol/L) 1
• Consider statin therapy if lifestyle modifications fail after 3-6 months 1

Special Populations

Diabetes Mellitus 1:

• Type 1 or Type 2 with CVD/CKD or age >40 with risk factors: LDL-C goal <70 mg/dL with high-intensity statin 1
• Type 2 without additional risk factors: LDL-C goal <100 mg/dL 1
• Measure lipids annually or every 2 years if at goal 1

Familial Hypercholesterolemia 1:

• Heterozygous FH: High-intensity statin plus ezetimibe as first-line therapy 1
• Homozygous FH: High-intensity statin plus ezetimibe, often requiring additional therapies (PCSK9 inhibitors, lomitapide, mipomersen, or LDL apheresis) 1

Hypertriglyceridemia 1:

• Mild to moderate (150-999 mg/dL): Optimize glycemic control first, lifestyle modifications, consider fibrates (gemfibrozil or fenofibrate) or high-dose omega-3 fatty acids 1
• Severe to very severe (≥1,000 mg/dL): Immediate fibrate therapy to prevent pancreatitis, strict dietary fat restriction (<15% of calories), avoid alcohol 1
• Non-HDL-C goal: 30 mg/dL higher than LDL-C goal 1

Combined Hyperlipidemia 1:

• First choice: High-dose statin plus improved glycemic control 1
• Second choice: Statin plus fibrate (monitor for myopathy risk) 1

Monitoring for Adverse Effects

Monitor for statin-related myopathy by instructing patients to report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. 1, 3

• Check baseline liver enzymes (ALT, AST) before initiating therapy 3
• Monitor liver function as clinically indicated; discontinue if persistent transaminase elevations >3× upper limit of normal or if hepatic injury with symptoms occurs 3
• Check CK levels if myopathy symptoms develop; discontinue statin if markedly elevated or if rhabdomyolysis suspected 3
• Monitor HbA1c and fasting glucose as statins may increase diabetes risk 3
• Temporarily discontinue statins in patients with acute conditions predisposing to renal failure 3

Adherence Strategies

Implement specific strategies to improve medication adherence. 1

• Agree on rather than dictate the treatment regimen 1
• Simplify dosing with once-daily regimens or fixed-dose combinations 1
• Provide written instructions and information on common side effects 1
• Encourage self-monitoring and use reminder technologies 1
• Involve family members or caregivers in treatment 1
• Perform regular medication reviews to minimize polypharmacy 1

Follow-Up

Assess LDL-C response as early as 4 weeks after initiating or adjusting therapy, then every 3-6 months until goal achieved, then annually. 1, 3

Monitoring Schedule

• Initial response: Check lipid panel 4-6 weeks after starting or changing therapy 1, 3
• Titration phase: Reassess every 6 weeks to 3 months until LDL-C goal achieved 1
• Maintenance: Annual lipid panel once at goal 1
• Hypertriglyceridemia: More frequent monitoring may be needed, especially with severe elevations 1

Treatment Adjustments

• If LDL-C goal not achieved: Increase statin dose, add ezetimibe, or consider PCSK9 inhibitor 1
• If statin intolerance: Try alternate statin, reduce dose, use alternate-day dosing, or switch to non-statin therapy (ezetimibe, bile acid sequestrants) 1
• Reassess cardiovascular risk periodically, especially if new risk factors develop 1

Common Pitfalls to Avoid

• Do not delay statin therapy in very high-risk patients (documented CVD, ACS) waiting for lifestyle modification trials 1
• Do not use statins alone for severe hypertriglyceridemia (≥1,000 mg/dL); fibrates are first-line to prevent pancreatitis 1
• Do not ignore secondary causes; treating underlying conditions (hypothyroidism, diabetes) may significantly improve lipid levels 1
• Do not assume all muscle symptoms are statin-related; most symptoms in blinded trials are not pharmacologically caused by statins 1
• Do not combine statins with gemfibrozil or fenofibrate without careful monitoring for myopathy risk 1
• Do not prescribe statins to pregnant or breastfeeding women 3