When should lipoprotein(a) (Lp(a)) be used in screening for cardiovascular disease?

Lipoprotein(a) Screening for Cardiovascular Disease

Lipoprotein(a) should be measured in patients with premature cardiovascular disease, familial hypercholesterolemia, family history of premature CVD, recurrent cardiovascular events despite optimal lipid-lowering therapy, and those with intermediate to high cardiovascular risk. 1, 2

Patient Populations Recommended for Lp(a) Screening

Primary Screening Recommendations

• Patients with premature cardiovascular disease (CVD) or stroke, particularly when other risk factors fail to explain the presence of vascular disease 1, 2
• Patients with familial hypercholesterolemia (FH) or other forms of genetic dyslipidemia 1, 2
• Patients with a family history of premature CVD or elevated Lp(a) 1, 2
• Patients with recurrent or rapidly progressive vascular disease despite optimal lipid-lowering therapy 1, 2

Secondary Screening Recommendations

• Patients who fall into intermediate risk categories according to standard risk algorithms (Framingham, PROCAM, ESC Heart Score, Australian/New Zealand risk calculators) 1
• Patients with ≥3% 10-year risk of fatal CVD according to European guidelines or ≥10% 10-year risk of fatal + non-fatal CHD according to US guidelines 1, 2
• Patients with low HDL-C 1
• Patients with genetic defects related to hemostasis and homocysteine metabolism 1
• Patients with diabetes mellitus and autoimmune diseases 1
• Patients with renal disease or on hemodialysis (Lp(a) is typically 2-3 fold elevated in these populations) 1

Interpretation of Lp(a) Levels

• Traditional thresholds for elevated Lp(a) are >30 mg/dL or >75 nmol/L, which represent approximately the 75th percentile in white populations 1, 2
• European guidelines suggest significant risk when Lp(a) levels are >50 mg/dL (>80th percentile) 1, 2
• The Canadian Cardiovascular Society uses a cutoff of >30 mg/dL to define abnormal Lp(a) levels 1, 2
• Risk assessment should consider various Lp(a) cutoffs (>30, >50-60, and >100 mg/dL) to identify patients most likely to benefit from Lp(a) lowering 2
• Patients with both elevated Lp(a) and elevated LDL cholesterol have a substantially higher risk (up to 10-fold) for myocardial infarction 1

Clinical Implications of Elevated Lp(a)

• Elevated Lp(a) is causally related to premature cardiovascular disease and represents one of the strongest genetic risk factors for vascular diseases 1, 3
• Lp(a) contributes to residual cardiovascular risk even when LDL-C is well-controlled 2, 4
• Patients with Lp(a) >50 mg/dL should be re-stratified into a higher risk category, which should lead to more intensive management of treatable risk factors, especially LDL cholesterol 1
• Children with elevated Lp(a) levels have a fourfold increased risk of acute ischemic stroke 2
• The risk of recurrent ischemic strokes is increased by more than 10-fold in patients with Lp(a) >90th percentile 2

Management Approach for Elevated Lp(a)

• The primary focus should be intensive management of traditional modifiable risk factors (LDL cholesterol, hypertension, smoking, diabetes, obesity) 1, 4
• Reducing LDL-C to the lowest attainable value with high-potency statins should be the primary lipid-modifying strategy 4, 5
• Niacin (up to 2-3 g/day) can reduce Lp(a) by 30-35% and may be considered in selected patients with elevated Lp(a) 1, 4
• LDL apheresis is effective in removing Lp(a) (up to 80% reduction) and may be considered in extreme cases with progressive coronary heart disease despite optimal therapy 1, 4
• Newer therapies targeting Lp(a) are under development, including antisense oligonucleotides and small interfering RNA molecules 3, 5

Common Pitfalls to Avoid

• Failing to measure Lp(a) in high-risk patients, particularly those with premature or recurrent cardiovascular disease 2
• Relying solely on LDL-C targets in patients with elevated Lp(a) may not adequately address Lp(a)-mediated risk 2, 4
• Overlooking that Lp(a)-C content is included in standard "LDL-C" laboratory measurements, potentially affecting achievement of LDL-C targets 1, 2
• Using non-standardized Lp(a) assays that may be affected by apo(a) isoform size 1
• Failing to recognize that conventional therapies like statins have limited or inconsistent effects on Lp(a) levels and may even increase Lp(a) in some cases 1, 2