What are the management recommendations for a 65‑year‑old woman with a total cholesterol (TC) of 296 mg/dL and a low‑density lipoprotein cholesterol (LDL‑C) of 186 mg/dL?

Management of Severe Hypercholesterolemia in a 65-Year-Old Woman

This patient requires immediate initiation of high-intensity statin therapy without calculating her 10-year ASCVD risk, as her LDL-C of 186 mg/dL meets the threshold for severe primary hypercholesterolemia. 1

Primary Recommendation: High-Intensity Statin Therapy

• Start high-intensity statin therapy immediately (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) targeting at least a 50% reduction in LDL-C from baseline. 1

• The ACC/AHA guidelines explicitly state that adults with LDL-C ≥190 mg/dL should receive high-intensity statin therapy without calculating 10-year ASCVD risk, as this population has markedly elevated lifetime ASCVD risk due to prolonged exposure to severely elevated LDL-C levels. 1

• At age 65, this patient falls within the 40-75 year age range where statin therapy has robust evidence for cardiovascular event reduction, with relative risk reductions similar to younger populations. 1

Exclude Secondary Causes Before Labeling as Primary Hypercholesterolemia

Before finalizing the diagnosis of primary severe hypercholesterolemia, evaluate for secondary causes that could elevate lipids: 1

• Hypothyroidism – check TSH
• Nephrotic syndrome or chronic kidney disease – check urinalysis for proteinuria, serum creatinine
• Biliary obstruction – assess liver function tests
• Medications – review for diuretics, cyclosporine, glucocorticoids, amiodarone
• Diabetes mellitus (poorly controlled) – check hemoglobin A1C if not already done

Consider Familial Hypercholesterolemia (FH)

• With an LDL-C of 186 mg/dL at age 65, evaluate for clinical features of heterozygous familial hypercholesterolemia using Simon Broome or Dutch Lipid Clinic criteria. 1

• Ask specifically about: family history of premature ASCVD (male relatives <55 years, female relatives <65 years), personal history of premature coronary disease, presence of tendon xanthomas, and corneal arcus before age 45. 1

• If FH is suspected, consider reverse-cascade screening of first-degree relatives. 1

Treatment Targets and Monitoring

• Target LDL-C reduction of ≥50% from baseline (from 186 mg/dL to <93 mg/dL). 1

• If the patient achieves only a 30-40% reduction on high-intensity statin monotherapy and LDL-C remains ≥100 mg/dL, adding ezetimibe 10 mg daily is reasonable to achieve further LDL-C lowering. 1

• Measure fasting lipid panel 4-12 weeks after statin initiation to assess adherence and percentage LDL-C reduction, along with appropriate safety indicators (ALT, CK if symptomatic). 1

• Repeat lipid measurements every 3-12 months thereafter based on adherence and achievement of treatment goals. 1

If LDL-C Remains ≥100 mg/dL on Maximally Tolerated Statin Plus Ezetimibe

• In patients with severe primary hypercholesterolemia (baseline LDL-C ≥190 mg/dL) whose LDL-C remains ≥100 mg/dL on statin plus ezetimibe and who have multiple factors that increase subsequent ASCVD risk, adding a PCSK9 inhibitor (evolocumab or alirocumab) may be considered, though long-term safety beyond 3 years is uncertain and cost-effectiveness remains low. 1

• Multiple risk-enhancing factors include: family history of premature ASCVD, metabolic syndrome, chronic kidney disease, chronic inflammatory disorders, or history of premature menopause. 1, 2

Mandatory Lifestyle Modifications

• Emphasize heart-healthy lifestyle as the foundation of ASCVD prevention, regardless of pharmacotherapy. 1

• Specific dietary recommendations: reduce saturated fat to <7% of total calories, limit cholesterol intake to <200 mg/day, eliminate trans fats, and increase intake of plant stanols/sterols and soluble fiber. 1

• Encourage at least 150 minutes per week of moderate-intensity aerobic physical activity. 1

• If overweight (BMI ≥25 kg/m²), target weight reduction to achieve BMI 18.5-24.9 kg/m² and waist circumference <35 inches for women. 1

Special Considerations for Age 65

• Although this patient is 65 years old, she falls within the 40-75 year age range where high-intensity statin therapy for LDL-C ≥190 mg/dL carries a Class I recommendation with strong evidence. 1

• Primary prevention statin trials have demonstrated significant ASCVD event reduction in adults aged 66-75 years, with relative risk reductions comparable to younger individuals. 1

• The mandatory clinician-patient risk discussion should address potential benefits (20-30% relative risk reduction in cardiovascular events), potential adverse effects (myalgias occur in ~5-10% of patients, new-onset diabetes risk ~0.3 excess cases per 100 patients per year on high-intensity statins), drug-drug interactions, and patient preferences. 1

Critical Pitfalls to Avoid

• Do not delay statin initiation to "try lifestyle modifications first" in a patient with LDL-C ≥190 mg/dL—pharmacotherapy should begin immediately alongside lifestyle counseling. 1

• Do not start with moderate-intensity statin therapy in this population; the guidelines explicitly recommend high-intensity statins for LDL-C ≥190 mg/dL. 1

• Do not use 10-year ASCVD risk calculation to decide whether to treat—the LDL-C threshold of ≥190 mg/dL overrides risk calculation and mandates treatment. 1

• Do not forget to assess for statin intolerance if the patient reports muscle symptoms; strategies include switching statins, reducing dose with addition of ezetimibe, or intermittent dosing regimens. 3