Should I order a lipoprotein(a) test in a young adult with LDL‑cholesterol 195 mg/dL (suspected familial hypercholesterolemia)?

Should You Order Lipoprotein(a) Testing in This Young Adult?

Yes, you should order a lipoprotein(a) test in this young adult with LDL-cholesterol 195 mg/dL and suspected familial hypercholesterolemia.

Rationale for Lp(a) Testing in Suspected FH

Lp(a) measurement is clinically important in this scenario because elevated Lp(a) levels significantly amplify cardiovascular risk in patients with familial hypercholesterolemia and can account for up to one-quarter of clinical FH diagnoses. 1

Why Lp(a) Matters in FH Diagnosis and Risk Stratification

• Elevated Lp(a) levels exacerbate the already high cardiovascular risk associated with familial hypercholesterolemia, particularly when combined with extreme LDL-cholesterol elevations 2

• Individuals with both FH and elevated Lp(a) have an extremely high risk of myocardial infarction, making identification of this combination critical for aggressive management 1

• Lp(a) is co-measured in standard LDL-cholesterol calculations, meaning that part of this patient's LDL-cholesterol of 195 mg/dL may actually represent Lp(a)-cholesterol content 1

• The European Heart Journal recommends measuring Lp(a) once in subjects with premature CVD, familial hypercholesterolemia, or a family history of premature CVD and/or elevated Lp(a) 3

Specific Indications for Lp(a) Testing in This Case

This young adult meets multiple criteria for Lp(a) screening:

• LDL-cholesterol ≥190 mg/dL strongly suggests familial hypercholesterolemia, which is a primary indication for Lp(a) measurement 4, 3

• Patients with suspected or confirmed FH should have Lp(a) measured to assess additional cardiovascular risk and guide treatment intensity 5, 3

• The Mayo Clinic recommends Lp(a) screening in patients with personal or family history of premature cardiovascular disease, familial hypercholesterolemia, or inadequate LDL-cholesterol responses to statins 5

Clinical Impact on Management

• If Lp(a) is elevated (≥50 mg/dL or ≥80th percentile), more aggressive LDL-cholesterol lowering targets are warranted 6, 3

• Elevated Lp(a) >300 mg/dL specifically requires more aggressive LDL-cholesterol lowering strategies 6

• The presence of elevated Lp(a) may influence the decision to initiate earlier or more intensive lipid-lowering therapy, even in the absence of other traditional risk factors 3

• Niacin (1-3 g/day) can be considered if Lp(a) is ≥30 mg/dL and residual LDL-cholesterol remains elevated despite maximum statin therapy 5, 3

Comprehensive Diagnostic Approach for This Patient

Confirm FH Diagnosis

• Measure LDL-cholesterol on at least two separate occasions (>2 weeks but <3 months apart) to confirm the diagnosis 4

• Apply Dutch Lipid Clinic Network or Simon Broome criteria, which incorporate LDL-cholesterol levels, family history of premature coronary artery disease, and physical stigmata 4, 7

• Exclude secondary causes of hypercholesterolemia including hypothyroidism, nephrotic syndrome, and cholestatic liver disease 4

Genetic Testing Should Be Pursued

• Genetic testing is the most accurate diagnostic method and should be offered to this young adult, particularly if a first-degree relative has similar lipid abnormalities or premature coronary disease 4

• Testing should include targeted next-generation sequencing of LDLR, APOB, PCSK9, and LDLRAP1 genes 4

• Genetic confirmation enables cascade testing of family members, which is highly cost-effective 4, 7

Additional Risk Assessment

• Assess for family history of premature cardiovascular disease (men ≤55 years, women ≤65 years) 4

• Examine for physical stigmata including Achilles tendon xanthomas, xanthelasmas, or corneal arcus 4

• Measure HDL-cholesterol, as low HDL is a key risk factor for atherosclerotic cardiovascular disease in FH patients 7

Critical Pitfalls to Avoid

• Do not delay Lp(a) testing until after statin initiation, as statins can increase Lp(a) levels, making baseline assessment more difficult to interpret 2

• Do not assume that achieving LDL-cholesterol goals alone is sufficient—patients with elevated Lp(a) require more aggressive targets 6, 3

• Do not use Lp(a) testing to monitor treatment response, as it should be measured only once for risk stratification 3

• Ensure the laboratory uses an isoform-insensitive assay for accurate Lp(a) measurement 3

Immediate Next Steps

• Order a comprehensive lipid panel including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and lipoprotein(a) 3

• Refer to a specialist center with expertise in lipidology and genetics for comprehensive FH evaluation and management planning 4, 7

• Initiate high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) immediately upon confirming FH diagnosis, targeting ≥50% LDL-cholesterol reduction 6

• Plan for genetic testing and cascade screening of first-degree relatives 4